David Busija

Summary

Affiliation: Wake Forest University School of Medicine
Country: USA

Publications

  1. ncbi request reprint Effects of ATP-sensitive potassium channel activators diazoxide and BMS-191095 on membrane potential and reactive oxygen species production in isolated piglet mitochondria
    David W Busija
    Department of Physiology and Pharmacology, Wake Forest University Health Sciences, Medical Center Boulevard, Winston Salem, NC 27157, USA
    Brain Res Bull 66:85-90. 2005
  2. ncbi request reprint Adverse effects of reactive oxygen species on vascular reactivity in insulin resistance
    David W Busija
    Department of Physiology and Pharmacology, Wake Forest University Health Sciences, Winston Salem, NC 27157, USA
    Antioxid Redox Signal 8:1131-40. 2006
  3. pmc Mechanisms involved in the cerebrovascular dilator effects of N-methyl-d-aspartate in cerebral cortex
    David W Busija
    Department of Physiology and Pharmacology, Wake Forest University Health Sciences, Medical Center Boulevard, Winston Salem, NC 27157 1010, USA
    Brain Res Rev 56:89-100. 2007
  4. pmc Mechanisms involved in the cerebrovascular dilator effects of cortical spreading depression
    David W Busija
    Department of Physiology and Pharmacology, Wake Forest University Health Sciences, Medical Center Boulevard, Winston Salem, NC 27157 1010, USA
    Prog Neurobiol 86:379-95. 2008
  5. ncbi request reprint Targeting mitochondrial ATP-sensitive potassium channels--a novel approach to neuroprotection
    David W Busija
    Department of Physiology and Pharmacology, and Center for Investigative Neuroscience, Wake Forest University Health Sciences, Medical Center Boulevard, Winston Salem, NC 27157 1010, USA
    Brain Res Brain Res Rev 46:282-94. 2004
  6. ncbi request reprint Mechanisms of vascular dysfunctionin insulin resistance
    David W Busija
    Wake Forest University Health Sciences, Department of Physiology and Pharmacology, Winston Salem, NC 27157 1023, USA
    Curr Opin Investig Drugs 5:929-35. 2004
  7. ncbi request reprint Insulin resistance and associated dysfunction of resistance vessels and arterial hypertension
    D W Busija
    Department of Physiology and Pharmacology, Wake Forest University Health Sciences, Winston Salem, NC 27157, USA
    Minerva Med 96:223-32. 2005
  8. pmc Mitochondrial-mediated suppression of ROS production upon exposure of neurons to lethal stress: mitochondrial targeted preconditioning
    David W Busija
    Department of Physiology and Pharmacology, Wake Forest University Health Sciences, Winston Salem, NC NC 27157 1010, USA
    Adv Drug Deliv Rev 60:1471-7. 2008
  9. ncbi request reprint Activation of mitochondrial ATP-sensitive potassium channels prevents neuronal cell death after ischemia in neonatal rats
    Nishadi Rajapakse
    Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston Salem, NC 27157, USA
    Neurosci Lett 327:208-12. 2002
  10. ncbi request reprint Diazoxide pretreatment induces delayed preconditioning in astrocytes against oxygen glucose deprivation and hydrogen peroxide-induced toxicity
    Nishadi Rajapakse
    Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston Salem, North Carolina 27157, USA
    J Neurosci Res 73:206-14. 2003

Research Grants

Collaborators

Detail Information

Publications86

  1. ncbi request reprint Effects of ATP-sensitive potassium channel activators diazoxide and BMS-191095 on membrane potential and reactive oxygen species production in isolated piglet mitochondria
    David W Busija
    Department of Physiology and Pharmacology, Wake Forest University Health Sciences, Medical Center Boulevard, Winston Salem, NC 27157, USA
    Brain Res Bull 66:85-90. 2005
    ..We conclude that BMS-191095 has selective effects on mitoK(ATP) channels while diazoxide also increases ROS production probably via inhibition of SDH...
  2. ncbi request reprint Adverse effects of reactive oxygen species on vascular reactivity in insulin resistance
    David W Busija
    Department of Physiology and Pharmacology, Wake Forest University Health Sciences, Winston Salem, NC 27157, USA
    Antioxid Redox Signal 8:1131-40. 2006
    ..Nonetheless, the most effective approach appears to involve prevention of IR via adoption of a healthy lifestyle by young people...
  3. pmc Mechanisms involved in the cerebrovascular dilator effects of N-methyl-d-aspartate in cerebral cortex
    David W Busija
    Department of Physiology and Pharmacology, Wake Forest University Health Sciences, Medical Center Boulevard, Winston Salem, NC 27157 1010, USA
    Brain Res Rev 56:89-100. 2007
    ..Here we review the development and current status of this important field of research especially in respect to cerebrovascular responses to NMDA receptor activation...
  4. pmc Mechanisms involved in the cerebrovascular dilator effects of cortical spreading depression
    David W Busija
    Department of Physiology and Pharmacology, Wake Forest University Health Sciences, Medical Center Boulevard, Winston Salem, NC 27157 1010, USA
    Prog Neurobiol 86:379-95. 2008
    ....
  5. ncbi request reprint Targeting mitochondrial ATP-sensitive potassium channels--a novel approach to neuroprotection
    David W Busija
    Department of Physiology and Pharmacology, and Center for Investigative Neuroscience, Wake Forest University Health Sciences, Medical Center Boulevard, Winston Salem, NC 27157 1010, USA
    Brain Res Brain Res Rev 46:282-94. 2004
    ..However, little is known about the mechanisms involved. The purpose of this review is to detail the current state of knowledge about this important, emerging area of investigation, and to provide suggestions for future studies...
  6. ncbi request reprint Mechanisms of vascular dysfunctionin insulin resistance
    David W Busija
    Wake Forest University Health Sciences, Department of Physiology and Pharmacology, Winston Salem, NC 27157 1023, USA
    Curr Opin Investig Drugs 5:929-35. 2004
    ....
  7. ncbi request reprint Insulin resistance and associated dysfunction of resistance vessels and arterial hypertension
    D W Busija
    Department of Physiology and Pharmacology, Wake Forest University Health Sciences, Winston Salem, NC 27157, USA
    Minerva Med 96:223-32. 2005
    ..Nonetheless, the most effective approach appears to involve prevention of IR via adoption of a healthy lifestyle by young people...
  8. pmc Mitochondrial-mediated suppression of ROS production upon exposure of neurons to lethal stress: mitochondrial targeted preconditioning
    David W Busija
    Department of Physiology and Pharmacology, Wake Forest University Health Sciences, Winston Salem, NC NC 27157 1010, USA
    Adv Drug Deliv Rev 60:1471-7. 2008
    ....
  9. ncbi request reprint Activation of mitochondrial ATP-sensitive potassium channels prevents neuronal cell death after ischemia in neonatal rats
    Nishadi Rajapakse
    Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston Salem, NC 27157, USA
    Neurosci Lett 327:208-12. 2002
    ..Fluorescent studies indicated DIZ directly depolarized the mitochondria. In conclusion, selective opening of mK(ATP) prior to HI results in neuroprotection in immature rats...
  10. ncbi request reprint Diazoxide pretreatment induces delayed preconditioning in astrocytes against oxygen glucose deprivation and hydrogen peroxide-induced toxicity
    Nishadi Rajapakse
    Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston Salem, North Carolina 27157, USA
    J Neurosci Res 73:206-14. 2003
    ....
  11. ncbi request reprint Influence of hypoxia/ischemia on cerebrovascular responses to oxytocin in piglets
    F Bari
    Department of Physiology and Pharmacology, Bowman Gray School of Medicine, Wake Forest University, Winston Salem, N C 27157 1083, USA
    J Vasc Res 34:312-20. 1997
    ..We conclude that the absence of pial arteriolar dilation to oxytocin after ischemia and asphyxia indicates endothelial dysfunction which may be involved in the pathology of perinatal brain injury...
  12. ncbi request reprint Cyclooxygenase-2 mediates the development of cortical spreading depression-induced tolerance to transient focal cerebral ischemia in rats
    T Horiguchi
    Department of Physiology and Pharmacology, Wake Forest University Health Sciences, USA, and Department of Neurosurgery, National Hospital Organization Tokyo Medical Center, 2 5 1 Higashigaoka Meguro ku, Tokyo, Japan
    Neuroscience 140:723-30. 2006
    ..We conclude that NO-mediated cyclooxygenase-2 upregulation by cortical spreading depression protects the brain against ischemic damage...
  13. ncbi request reprint Inhibitors of protein synthesis preserve the N-methyl-D-aspartate-induced cerebral arteriolar dilation after ischemia in piglets
    R Veltkamp
    Stroke Research Center and Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston Salem, NC 27157 1083, USA
    Stroke 30:148-52. 1999
    ....
  14. ncbi request reprint Kainate-induced cerebrovascular dilation is resistant to ischemia in piglets
    F Bari
    Department of Physiology and Pharmacology, Bowman Gray School of Medicine, Wake Forest University, Winston Salem, NC 27157 1083, USA
    Stroke 28:1272-6; discussion 1277. 1997
    ..The purpose of this study was to examine the effects of ischemia on cerebral arteriolar responses to kainate in anesthetized piglets...
  15. ncbi request reprint Transient focal ischemia increases endothelial nitric oxide synthase in cerebral blood vessels
    Roland Veltkamp
    Department of Physiology and Pharmacology and Center for Investigative Neuroscience, Wake Forest University School of Medicine, Winston Salem, NC, USA
    Stroke 33:2704-10. 2002
    ..Production of NO by endothelial NO synthase (eNOS) plays a protective role in cerebral ischemia. We studied the effects of transient focal ischemia on eNOS expression...
  16. ncbi request reprint A mutation in the inner mitochondrial membrane peptidase 2-like gene (Immp2l) affects mitochondrial function and impairs fertility in mice
    Baisong Lu
    Institute for Regenerative Medicine, Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Wake Forest University Health Sciences, Winston Salem, North Carolina 27157, USA
    Biol Reprod 78:601-10. 2008
    ..The results provide a novel link between mitochondrial dysfunction and infertility and suggest that superoxide ion targeting agents may prove useful for treating infertility in a subpopulation of infertile patients...
  17. ncbi request reprint Chronic adrenomedullin treatment improves blood-brain barrier function but has no effects on expression of tight junction proteins
    B Kis
    Department of Physiology and Pharmacology, Wake Forest University, School of Medicine, Winston Salem, NC 27157, USA
    Acta Neurochir Suppl 86:565-8. 2003
    ....
  18. ncbi request reprint Cloning of cyclooxygenase-1b (putative COX-3) in mouse
    B Kis
    Department of Physiology and Pharmacology, Wake Forest University Health Sciences, Medical Center Blvd, Winston Salem, NC 27157, USA
    Inflamm Res 55:274-8. 2006
    ..To clone and sequence cyclooxygenase-1b (COX-1b, also known as COX-3) mRNA and to generate an antibody against the mouse COX-1b protein and to demonstrate its existence in vivo in mouse tissues...
  19. ncbi request reprint Mitochondrial nitric oxide synthase is constitutively active and is functionally upregulated in hypoxia
    Z Lacza
    Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston Salem, NC 27157, USA
    Free Radic Biol Med 31:1609-15. 2001
    ..We conclude that mtNOS is a constitutively active eNOS-like isoform and is involved in altered mitochondrial regulation during hypoxia...
  20. ncbi request reprint Potassium channel activators protect the N-methyl-D-aspartate-induced cerebral vascular dilation after combined hypoxia and ischemia in piglets
    R Veltkamp
    Stroke Research Center, Department of Physiology and Pharmacology, Bowman Gray School of Medicine, Wake Forest University, Winston Salem, NC 27157 1083, USA
    Stroke 29:837-42; discussion 842-3. 1998
    ..We tested the hypothesis that topical pretreatment with the selective potassium channel agonists NS1619 and aprikalim preserves the vascular response to NMDA after consecutive H/I...
  21. ncbi request reprint Endothelial nitric oxide synthase gene transfer enhances dilation of newborn piglet pulmonary arteries
    J L Aschner
    Department of Pediatrics, Wake Forest University School of Medicine, Winston Salem, North Carolina 27157 1081, USA
    Am J Physiol 277:H371-9. 1999
    ..Gene transfer with replication-deficient adenovirus vectors is a useful tool for the study of targeted genes in vascular biology...
  22. ncbi request reprint Cycloheximide rapidly inhibits cortical COX activity and COX-dependent pial arteriolar dilation in piglets
    F Domoki
    Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston Salem, North Carolina 27157 1010, USA
    Am J Physiol 277:H1113-8. 1999
    ..28 +/- 3.04 to 5.90 +/- 1.26 ng/ml (n = 9). Thus CHX rapidly decreases COX activity in the piglet cerebral cortex. This result may explain in part the preservation of neuronal function of CHX in cerebral ischemia...
  23. ncbi request reprint Ischemia-reperfusion rapidly increases COX-2 expression in piglet cerebral arteries
    F Domoki
    Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston Salem, North Carolina 27157 1083, USA
    Am J Physiol 277:H1207-14. 1999
    ..COX-1 mRNA levels were low in time controls, and ischemic stress had no significant effect on COX-1 expression. Thus ischemic stress leads to relatively rapid, selective induction of COX-2 in cerebral arteries...
  24. ncbi request reprint Cyclooxygenase-2 inhibitor NS398 preserves neuronal function after hypoxia/ischemia in piglets
    F Domoki
    Department of Physiology and Pharmacology, Center for Investigative Neuroscience, Wake Forest University School of Medicine, Medical Center Boulevard, Winston Salem, NC 27157-1010, USA
    Neuroreport 12:4065-8. 2001
    ..Indomethacin caused similar preservation. However, indomethacin but not NS398 reduced serum thromboxane B(2) levels to undetectable values. In conclusion, COX-2 appears to be a major source of ROS in the piglet cerebral cortex after H/I...
  25. ncbi request reprint Characteristics of induced spreading depression after transient focal ischemia in the rat
    K Shimizu
    Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston Salem, NC 27157 1083, USA
    Brain Res 861:316-24. 2000
    ..Further, our results indicate that nitric oxide does not promote CBF responses during SD in normal cortex or in tissue surrounding infarction...
  26. ncbi request reprint Modulation of prostaglandin production by nitric oxide in astroglia
    D W Busija
    Department of Physiology and Pharmacology, Bowman Gray School of Medicine, Wake Forest University, Winston Salem, NC 27157 1083, USA
    Prostaglandins Leukot Essent Fatty Acids 56:355-9. 1997
    ..In summary, application of 100 microM SNP reduces basal production of PGF2 alpha and attenuates increases in PGF2 alpha levels with IL1 alpha application...
  27. ncbi request reprint Epoxyeicosatrienoic acid-induced relaxation is impaired in insulin resistance
    A W Miller
    Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA
    Am J Physiol Heart Circ Physiol 281:H1524-31. 2001
    ..In contrast, arteries from IR rats do not relax to the EETs. Patch-clamp studies suggest impaired relaxation is due to altered regulatory mechanisms of the BK(Ca) channel...
  28. ncbi request reprint Hyperbaric oxygen decreases infarct size and behavioral deficit after transient focal cerebral ischemia in rats
    R Veltkamp
    Stroke Research Center, Wake Forest University School of Medicine, Winston Salem, NC 27157 1083, USA
    Brain Res 853:68-73. 2000
    ..Potential mechanisms include enhanced oxygen supply to marginally perfused cells...
  29. ncbi request reprint Immunofluorescent localization of constitutive and inducible prostaglandin H synthase in ovine astroglia
    C R Thore
    Department of Physiology and Pharmacology, Wake Forest University, Winston Salem, North Carolina 27157 1083, USA
    J Comp Neurol 367:1-9. 1996
    ..We conclude that astrocytes cultured in serum express both constitutive and inducible forms of PGHS and that PGHS-2 is induced by mitogens in this cell type...
  30. ncbi request reprint In vitro and in vivo localization of prostaglandin H synthase in fetal sheep neurons
    C R Thore
    Department of Physiology, Bowman Gray School of Medicine, Winston Salem, NC 27157 1083, USA
    Neurosci Lett 242:29-32. 1998
    ..Neuronal PGHS-2 IR extended into processes and amassed in growth cones and at the leading edge processes of astrocytes. Novel rosette formations, possibly lipid bodies, were common in cultured neurons, but not astrocytes...
  31. pmc Adaptation of the hypothalamic blood flow to chronic nitric oxide deficiency is independent of vasodilator prostanoids
    László Hortobágyi
    Institute of Human Physiology and Clinical Experimental Research, Semmelweis University, Budapest, Hungary
    Brain Res 1131:129-37. 2007
    ..Reduced release of vasoconstrictor prostanoids, however, may contribute to the normalization of HBF after chronic loss of NO...
  32. ncbi request reprint Rosuvastatin improves cerebrovascular function in Zucker obese rats by inhibiting NAD(P)H oxidase-dependent superoxide production
    Benedek Erdos
    Department of Physiology and Pharmacology, Wake Forest University Health Sciences, Medical Center Blvd, Winston Salem, North Carolina 27157 1083, USA
    Am J Physiol Heart Circ Physiol 290:H1264-70. 2006
    ..These findings demonstrate that RSV improves cerebrovascular function in insulin-resistance independently from its lipid-lowering effect by the inhibition of NAD(P)H oxidase...
  33. ncbi request reprint Cortical spreading depression (CSD)-induced tolerance to transient focal cerebral ischemia in halothane anesthetized rats is affected by anesthetic level but not ATP-sensitive potassium channels
    Takashi Horiguchi
    Department of Physiology and Pharmacology, Wake Forest University Health Sciences, Medical Center Boulevard, Winston Salem, NC 27157 1083, USA
    Brain Res 1062:127-33. 2005
    ..These results uncover a crucial role of halothane level but not of K(ATP) channels or adenosine A1 receptors in the preconditioning effects of CSD...
  34. ncbi request reprint Acetazolamide induces indomethacin and ischaemia-sensitive pial arteriolar vasodilation in the piglet
    Ferenc Domoki
    Department of Physiology, University of Szeged, Szeged, Hungary
    Acta Paediatr 97:280-4. 2008
    ..The underlying mechanism is unclear, but it is assumed to be largely due to CO2 retention and acidosis. We tested if cerebrovascular effects of AZD were similar to hypercapnia in the newborn pig...
  35. ncbi request reprint Diazoxide preconditioning attenuates global cerebral ischemia-induced blood-brain barrier permeability
    Gabor Lenzser
    Department of Physiology and Pharmacology, Wake Forest University Health Sciences, Winston Salem, NC 27157 1010, USA
    Brain Res 1051:72-80. 2005
    ..Our results demonstrate that preconditioning of cerebral endothelium with diazoxide protects the BBB against ischemic stress...
  36. ncbi request reprint Effects of LPS stimulation on the expression of prostaglandin carriers in the cells of the blood-brain and blood-cerebrospinal fluid barriers
    Bela Kis
    Department of Physiology and Pharmacology, Wake Forest University Health Sciences, Medical Center Boulevard, Winston Salem, NC 27157, USA
    J Appl Physiol (1985) 100:1392-9. 2006
    ....
  37. ncbi request reprint Kynurenic acid attenuates NMDA-induced pial arteriolar dilation in newborn pigs
    Ferenc Bari
    Department of Physiology, Faculty of Medicine, University of Szeged, Dom ter 10, H 6720 Szeged, Hungary
    Brain Res 1069:39-46. 2006
    ..5-2 h) following an episode of cerebral ischemia. Our data are relevant for the use of drugs that target the kynurenine pathway for therapeutic interventions in cerebrovascular diseases...
  38. ncbi request reprint Piglet pial arteries respond to N-methyl-D-aspartate in vivo but not in vitro
    Steve A Simandle
    Department of Pediatrics, Division of Neonatology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston Salem, NC 27157 1010, USA
    Microvasc Res 70:76-83. 2005
    ..This work confirms our previous in vivo data and is consistent with the hypothesis that cerebral arteries respond to NMDA through a secondary interaction mediated by neuronal release of NO and not to NMDA directly...
  39. ncbi request reprint Insulin resistance does not impair contractile responses of cerebral arteries
    Steve A Simandle
    Department of Physiology and Pharmacology, Wake Forest University Health Sciences, Winston Salem, North Carolina 27157, United States
    Life Sci 77:2262-72. 2005
    ....
  40. ncbi request reprint Adrenomedullin protects rat cerebral endothelial cells from oxidant damage in vitro
    Lei Chen
    Department of Physiology, School of Medicine, University of Occupational and Environmental Health, Iseigaoka 1 1, Yahatanishi ku, Kitakyushu 807 8555, Japan
    Regul Pept 130:27-34. 2005
    ..These results suggest that AM treatment protects CECs against oxidative injury...
  41. ncbi request reprint Impaired endothelin-induced vasoconstriction in coronary arteries of Zucker obese rats is associated with uncoupling of [Ca2+]i signaling
    Prasad V G Katakam
    Deptartment of Physiology and Pharmacology, Wake Forest University Health Sciences, Hanes 1050, Medical Center Blvd, Winston Salem, NC 27157, USA
    Am J Physiol Regul Integr Comp Physiol 290:R145-53. 2006
    ..Thus coronary arteries from ZO rats exhibit reduced ET-1-induced vasoconstriction resulting from increased ET(B)-mediated generation of NO and diminished elevation of myoplasmic [Ca2+]i...
  42. ncbi request reprint ROS-independent preconditioning in neurons via activation of mitoK(ATP) channels by BMS-191095
    Tamas Gaspar
    Department of Physiology and Pharmacology, Wake Forest University Health Sciences, Medical Center Boulevard, Winston Salem, NC 27157 1010, USA
    J Cereb Blood Flow Metab 28:1090-103. 2008
    ..These mechanisms appear to play important roles in the neuroprotective effect of BMS...
  43. ncbi request reprint Contribution of poly(ADP-ribose) polymerase to postischemic blood-brain barrier damage in rats
    Gabor Lenzser
    Department of Physiology and Pharmacology, Wake Forest University Health Sciences, Winston Salem, North Carolina 27157
    J Cereb Blood Flow Metab 27:1318-26. 2007
    ..The inhibition of PARP activity accompanied by reduced post-ischemic BBB disturbance and decreased edema formation suggests a significant role of this enzyme in the development of cerebral vascular malfunction..
  44. ncbi request reprint Human heart mitochondria do not produce physiologically relevant quantities of nitric oxide
    Attila Csordas
    Department of Human Physiology and Clinical Experimental Research, Semmelweis University, Budapest, Hungary
    Life Sci 80:633-7. 2007
    ..These results indicate that mitochondria do not produce physiologically relevant quantities of NO in the heart and are unlikely to have any physiological importance as NO donors, nor do they contain a recognizable mtNOS enzyme...
  45. ncbi request reprint Myocardial preconditioning against ischemia-reperfusion injury is abolished in Zucker obese rats with insulin resistance
    Prasad V G Katakam
    Department of Physiology and Pharmacology, Wake Forest University Health Sciences, Hanes 1050, Medical Center Blvd, Winston Salem, NC 27157, USA
    Am J Physiol Regul Integr Comp Physiol 292:R920-6. 2007
    ..Thus obesity accompanied by IR is associated with the inability to precondition against ischemic cardiac injury, which is mediated by enhanced mitochondrial oxidative stress and impaired activation of mitochondrial K(ATP)...
  46. ncbi request reprint Neuronal preconditioning with the antianginal drug, bepridil
    Tamas Gaspar
    Department of Physiology and Pharmacology, Wake Forest University Health Sciences, Winston Salem, North Carolina 27157 1010, USA
    J Neurochem 102:595-608. 2007
    ..Our results indicate that BEP induces delayed neuronal preconditioning which is dependent on superoxide generation but perhaps not on direct mitoK(ATP) activation...
  47. ncbi request reprint Transient glucose and amino acid deprivation induces delayed preconditioning in cultured rat cortical neurons
    Tamas Gaspar
    Department of Physiology and Pharmacology, Wake Forest University Health Sciences, Winston Salem, North Carolina 27157 1010, USA
    J Neurochem 98:555-65. 2006
    ..Our findings show that transient energy deprivation induces delayed preconditioning and prevents oxidative injuries and neuronal cell death...
  48. ncbi request reprint The mitochondrial K(ATP) channel opener BMS-191095 reduces neuronal damage after transient focal cerebral ischemia in rats
    Keita Mayanagi
    Department of Physiology and Pharmacology, Wake Forest University Health Sciences, Medical Center Boulevard, Winston Salem, North Carolina 27157 1010, USA
    J Cereb Blood Flow Metab 27:348-55. 2007
    ..Thus, BMS-191095 afforded protection against cerebral ischemia by delayed preconditioning via selective opening of mitoK(ATP) channels and without ROS generation...
  49. ncbi request reprint Adrenomedullin 2 protects rat cerebral endothelial cells from oxidative damage in vitro
    Lei Chen
    Department of Physiology, School of Medicine, University of Occupational and Environmental Health, Iseigaoka 1 1, Kitakyushu 807 8555, Japan
    Brain Res 1086:42-9. 2006
    ..These effects of AM2 were similar to those what were reported for adrenomedullin. These results suggest that AM2 protects CECs against oxidative injury in vitro...
  50. ncbi request reprint Pituitary adenylate cyclase-activating polypeptide induces pial arteriolar vasodilation through cyclooxygenase-dependent and independent mechanisms in newborn pigs
    Laura Lenti
    Department of Physiology, Faculty of Medicine, University of Szeged, 6720 Szeged, Dom ter 10, Hungary
    Brain Res 1165:81-8. 2007
    ..In summary, PACAP27 and 38 are potent vasodilators in the neonatal cerebral circulation with at least two distinct mechanisms of action: a COX-dependent and a COX-independent pathway...
  51. ncbi request reprint Systemic administration of diazoxide induces delayed preconditioning against transient focal cerebral ischemia in rats
    Keita Mayanagi
    Department of Physiology and Pharmacology, Wake Forest University Health Sciences, Medical Center Boulevard, Winston Salem, NC 27157 1010, USA
    Brain Res 1168:106-11. 2007
    ..These findings support the concept that diazoxide produces delayed preconditioning via mitoK(ATP) activation but that physiological status can affect induction of preconditioning...
  52. pmc Delayed neuronal preconditioning by NS1619 is independent of calcium activated potassium channels
    Tamas Gaspar
    Department of Physiology and Pharmacology, Wake Forest University Health Sciences, Medical Center Boulevard, Winston Salem, North Carolina, USA
    J Neurochem 105:1115-28. 2008
    ..However, the neuroprotective effect seems to be independent of cell membrane and mitochondrial BK(Ca) channels. Rather it is the consequence of ROS generation, activation of the PI3K pathway, and inhibition of caspase activation...
  53. ncbi request reprint Acetaminophen and the cyclooxygenase-3 puzzle: sorting out facts, fictions, and uncertainties
    Bela Kis
    Department of Physiology and Pharmacology, Wake Forest University Health Sciences, Medical Center Boulevard, Winston Salem, NC 27157, USA
    J Pharmacol Exp Ther 315:1-7. 2005
    ..The aim of this review is to evaluate the literature that seeks to point out critical theoretical and methodological limitations of the COX-3 studies that led several investigators to scientifically questionable conclusions...
  54. ncbi request reprint The role of nitric oxide in the development of cortical spreading depression-induced tolerance to transient focal cerebral ischemia in rats
    Takashi Horiguchi
    Department of Physiology and Pharmacology, Wake Forest University Health Sciences, Medical Center Boulevard, Winston Salem, NC 27157 1083, USA
    Brain Res 1039:84-9. 2005
    ..Those responses are significantly augmented by L-NAME (3-fold for ERK and 4-fold for COX-2). These results suggest a crucial role of NO in the establishment of preconditioning with CSD...
  55. ncbi request reprint Diazoxide preserves hypercapnia-induced arteriolar vasodilation after global cerebral ischemia in piglets
    Ferenc Domoki
    Dept of Physiology, Faculty of Medicine, Univ of Szeged, Szeged, Dom ter 10, H 6720 Hungary
    Am J Physiol Heart Circ Physiol 289:H368-73. 2005
    ..In summary, preservation of arteriolar dilator responsiveness by Diaz may contribute to neuroprotection...
  56. ncbi request reprint Fructose-fed rats are protected against ischemia/reperfusion injury
    James E Jordan
    Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Hanes 1050, Medical Center Boulevard, Winston Salem, NC 27157, USA
    J Pharmacol Exp Ther 307:1007-11. 2003
    ..This study suggests that fructose feeding affords protection against MI/R that is related to or mimics preconditioning. This protection is not consistent with other models of IR and is likely related to the fructose diet itself...
  57. ncbi request reprint PARP inhibition improves the effectiveness of neural stem cell transplantation in experimental brain trauma
    Zsombor Lacza
    Department of Physioloty Pharmacology, Wake Forest University School of Medicine, Winston Salem, NC 27157, USA
    Int J Mol Med 12:153-9. 2003
    ..Inhibition of the ONOO- - PARP activation cascade significantly improves the effectiveness of neural stem cell transplantation and promotes rapid functional recovery...
  58. ncbi request reprint Neuroprotection against hypoxia-ischemia in neonatal rat brain by novel superoxide dismutase mimetics
    Katsuyoshi Shimizu
    Departments of Physiology and Pharmacology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston Salem, NC 27157 1083, USA
    Neurosci Lett 346:41-4. 2003
    ..05, n=8). These data indicate that the SOD mimetics M40403 and M40401 have protective effects against hypoxic-ischemic brain injury, and suggest the involvement of superoxide anion in neuronal cell injury during H/I...
  59. ncbi request reprint Opening of mitochondrial ATP-sensitive potassium channels is a trigger of 3-nitropropionic acid-induced tolerance to transient focal cerebral ischemia in rats
    Takashi Horiguchi
    Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston Salem, NC 27157 1083, USA
    Stroke 34:1015-20. 2003
    ....
  60. ncbi request reprint Adrenomedullin, an autocrine mediator of blood-brain barrier function
    Bela Kis
    Department of Physiology and Pharmacology, Wake Forest University, Medical Center Boulevard, Winston Salem, NC 27157, USA
    Hypertens Res 26:S61-70. 2003
    ....
  61. ncbi request reprint Protective effect of a new nonpeptidyl mimetic of SOD, M40401, against focal cerebral ischemia in the rat
    Katsuyoshi Shimizu
    Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Medical Center Blvd, Winston Salem, NC 27157 1083, USA
    Brain Res 963:8-14. 2003
    ..These data indicate that M40401 protects cerebral tissue from ischemic insult when administered before MCAO, probably by limiting damage mediated by detrimental actions of superoxide anion...
  62. ncbi request reprint Arachidonic acid-induced vasodilation of rat small mesenteric arteries is lipoxygenase-dependent
    Allison W Miller
    Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston Salem, North Carolina 27157, USA
    J Pharmacol Exp Ther 304:139-44. 2003
    ..These findings provide functional and biochemical evidence that the lipoxygenase pathway mediates arachidonic acid-induced vasodilation in rat small mesenteric arteries through a K+ channel-dependent mechanism...
  63. ncbi request reprint Effects of hypothermia on neuronal-vascular function after cerebral ischemia in piglets
    James V Perciaccante
    Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill 27599, USA
    Am J Physiol Regul Integr Comp Physiol 283:R1362-7. 2002
    ..20 +/- 5%; n = 10). In contrast, pretreatment with indomethacin resulted in complete preservation of NMDA-induced vasodilation after ischemia. Thus, hypothermia fails to protect against neuronal dysfunction during ischemia...
  64. ncbi request reprint Alterations in KATP and KCa channel function in cerebral arteries of insulin-resistant rats
    Benedek Erdos
    Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston Salem, North Carolina 27157 1083, USA
    Am J Physiol Heart Circ Physiol 283:H2472-7. 2002
    ..01). These findings demonstrate that insulin resistance alters the function of K(ATP) and K(Ca) channels in isolated MCAs and affects the control of resting vascular tone and the mediation of dilator stimuli...
  65. ncbi request reprint MitoK(ATP) opener, diazoxide, reduces neuronal damage after middle cerebral artery occlusion in the rat
    Katsuyoshi Shimizu
    Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston Salem, North Carolina 27157 1083, USA
    Am J Physiol Heart Circ Physiol 283:H1005-11. 2002
    ..These results indicate that selective opening of the mitoK(ATP) channel has neuroprotective effects against ischemia-reperfusion injury in the rat brain...
  66. ncbi request reprint Enhanced endothelin activity prevents vasodilation to insulin in insulin resistance
    Allison W Miller
    Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston Salem, NC 27157, USA
    Hypertension 40:78-82. 2002
    ..Thus, impaired relaxation to insulin in insulin-resistant rats is due to enhanced vasoconstriction by endothelin, which offsets a normal vasodilatory response to insulin...
  67. ncbi request reprint Hydrogen peroxide acts as an EDHF in the piglet pial vasculature in response to bradykinin
    Zsombor Lacza
    Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston Salem, North Carolina 27157, USA
    Am J Physiol Heart Circ Physiol 283:H406-11. 2002
    ..We conclude that H(2)O(2) mediates the non-nitric oxide-, non-prostanoid-dependent vasorelaxation to BK in the piglet pial vasculature. The response is mediated via BK(2) receptors and the opening of K(ATP) channels...
  68. ncbi request reprint Impaired endothelium-mediated relaxation in isolated cerebral arteries from insulin-resistant rats
    Benedek Erdos
    Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston Salem, North Carolina 27157 1083, USA
    Am J Physiol Heart Circ Physiol 282:H2060-5. 2002
    ..These findings demonstrate that endothelium-dependent dilation in cerebral arteries is impaired in IR primarily because of a defect of the COX-mediated pathways. In contrast, nitric oxide-mediated dilation remains intact in IR arteries...
  69. ncbi request reprint N-methyl-D-aspartate-induced vasodilation is mediated by endothelium-independent nitric oxide release in piglets
    Ferenc Domoki
    Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston Salem, North Carolina 27157 1010, USA
    Am J Physiol Heart Circ Physiol 282:H1404-9. 2002
    ..In conclusion, NMDA appears to dilate pial arterioles exclusively through release and diffusion of NO from neurons to the pial surface in piglets...
  70. ncbi request reprint Heart mitochondria contain functional ATP-dependent K+ channels
    Zsombor Lacza
    Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston Salem, NC 27157, USA
    J Mol Cell Cardiol 35:1339-47. 2003
    ..We conclude that a functional K(ATP) channel is present in heart mitochondria, which can be opened by diazoxide or BMS-191095. The channel can be composed of Kir6.1 and Kir6.2 subunits and does not contain either SUR1 or SUR2...
  71. ncbi request reprint Putative cyclooxygenase-3 expression in rat brain cells
    Bela Kis
    Department of Physiology and Pharmacology, Wake Forest University, School of Medicine, Winston Salem, NC 27157, USA
    J Cereb Blood Flow Metab 23:1287-92. 2003
    ..In summary, we report, for the first time to our knowledge, that the putative COX-3 mRNA is detectable in rats and is differentially expressed in various cell types from rat brain, as well as that its expression is not stimulated by LPS...
  72. ncbi request reprint Impaired insulin-induced vasodilation in small coronary arteries of Zucker obese rats is mediated by reactive oxygen species
    Prasad V G Katakam
    Department of Physiology and Pharmacology, Wake Forest University Health Sciences, Winston Salem, North Carolina 27157, USA
    Am J Physiol Heart Circ Physiol 288:H854-60. 2005
    ....
  73. ncbi request reprint Cloning and characterization of cyclooxygenase-1b (putative cyclooxygenase-3) in rat
    James A Snipes
    Department of Physiology and Pharmacology, Wake Forest University Health Sciences, Medical Center Blvd, Winston Salem, NC 27157, USA
    J Pharmacol Exp Ther 313:668-76. 2005
    ....
  74. ncbi request reprint Acetaminophen-sensitive prostaglandin production in rat cerebral endothelial cells
    Bela Kis
    Dept of Physiology and Pharmacology, Wake Forest Univ Health Sciences, Medical Center Boulevard, Winston Salem, NC 27157, USA
    Am J Physiol Regul Integr Comp Physiol 288:R897-902. 2005
    ..Furthermore, our findings support a critical role for cerebral endothelium in the therapeutic actions of acetaminophen in the central nervous system...
  75. ncbi request reprint Vasoconstrictor mechanisms in the cerebral circulation are unaffected by insulin resistance
    Benedek Erdos
    Department of Physiology and Pharmacology, Wake Forest University Health Sciences, Medical Center Blvd, Winston Salem, NC 27157 1083, USA
    Am J Physiol Regul Integr Comp Physiol 287:R1456-61. 2004
    ..01). These findings indicate that vasoconstrictor responses of the BA mediated by ET-1, TxA(2), PKC, and Rho-kinase are not affected by IR...
  76. ncbi request reprint Diazoxide prevents mitochondrial swelling and Ca2+ accumulation in CA1 pyramidal cells after cerebral ischemia in newborn pigs
    Ferenc Domoki
    Department of Physiology, Faculty of Medicine, University of Szeged, Szeged, Dóm tér 10 H 6720, Hungary
    Brain Res 1019:97-104. 2004
    ..44+/-1.98%). Thus, DIAZ might preserve mitochondrial integrity in CA1 pyramidal cells after I/R, at least in part mediated by mK(ATP)...
  77. ncbi request reprint Lack of mitochondrial nitric oxide production in the mouse brain
    Zsombor Lacza
    Department of Physiology Pharmacology, Wake Forest University School of Medicine, Winston Salem, North Carolina, USA
    J Neurochem 90:942-51. 2004
    ..We conclude that mouse brain mitochondria do not contain NOS isoforms, nor do they produce NO through a NOS-dependent mechanism...
  78. ncbi request reprint Regional distribution of cyclooxygenase-3 mRNA in the rat central nervous system
    Bela Kis
    Department of Physiology and Pharmacology, Wake Forest University Health Sciences, Medical Center Boulevard, Winston Salem, NC 27157, USA
    Brain Res Mol Brain Res 126:78-80. 2004
    ..Our results suggest that the expression pattern of COX-3 mRNA in the rat CNS primarily relates to the vascular density of a given region...
  79. ncbi request reprint Diazoxide preconditioning protects against neuronal cell death by attenuation of oxidative stress upon glutamate stimulation
    Krisztina Nagy
    Department of Physiology and Pharmacology, Wake Forest University Health Sciences, Winston Salem, North Carolina 27157, USA
    J Neurosci Res 76:697-704. 2004
    ..These results suggest that diazoxide induces delayed preconditioning in cultured cortical neurons via increased ROS production and attenuation of oxidative stress upon glutamate stimulation...
  80. ncbi request reprint Cerebrovascular dysfunction in Zucker obese rats is mediated by oxidative stress and protein kinase C
    Benedek Erdös
    Department of Physiology and Pharmacology, Wake Forest University Health Science, Medical Center Boulevard, Winston Salem, NC 27157 1083, USA
    Diabetes 53:1352-9. 2004
    ..The revealed impairment of NO and K+ channel-dependent dilator responses may be responsible for the increased risk of cerebrovascular events and neurodegenerative disorders in IR...
  81. ncbi request reprint The mitochondrial K(ATP) channel opener BMS-191095 induces neuronal preconditioning
    Bela Kis
    Department of Physiology and Pharmacology, Wake Forest University, School of Medicine, Medical Center Boulevard, Winston Salem, NC 27157, USA
    Neuroreport 15:345-9. 2004
    ....
  82. ncbi request reprint Rosuvastatin treatment reverses impaired coronary artery vasodilation in fructose-fed, insulin-resistant rats
    Allison W Miller
    Dept of Physiology and Pharmacology, Wake Forest Univ School of Medicine, Hanes 1050, Medical Center Blvd, Winston Salem, NC 27157, USA
    Am J Physiol Regul Integr Comp Physiol 287:R157-60. 2004
    ..Moreover, this recovery in function was due to an improvement in vasodilation via K(Ca). Thus rosuvastatin treatment of IR rats normalizes coronary vascular dilator responses by improving the K(Ca) function...
  83. ncbi request reprint Potassium channel dysfunction in cerebral arteries of insulin-resistant rats is mediated by reactive oxygen species
    Benedek Erdos
    Department of Physiology and Pharmacology, Wake Forest University Health Sciences, Medical Center Blvd, Winston Salem, NC 27157 1083, USA
    Stroke 35:964-9. 2004
    ..One possible underlying factor is cerebrovascular dysfunction resulting from altered K(+) channel function. Thus, the goal of this study was to examine K+ channel-mediated relaxation in IR cerebral arteries...
  84. ncbi request reprint Investigation of the subunit composition and the pharmacology of the mitochondrial ATP-dependent K+ channel in the brain
    Zsombor Lacza
    Department of Physiology Pharmacology, Wake Forest University School of Medicine, Winston Salem, NC 27157, USA
    Brain Res 994:27-36. 2003
    ..We conclude that brain mitochondria contain functional K(ATP) channels. The pore-forming subunit of the channel can be either Kir6.1 or Kir6.2, and the SUR subunit may be a SUR2 splice variant or a similar protein...
  85. ncbi request reprint Diazoxide induces delayed pre-conditioning in cultured rat cortical neurons
    Bela Kis
    Department of Physiology and Pharmacology, Wake Forest University, Winston Salem, North Carolina 27157, USA
    J Neurochem 87:969-80. 2003
    ..The succinate dehydrogenase-inhibiting effect of diazoxide is more likely to be involved in this neuroprotection than the opening of mitochondrial ATP-sensitive potassium channels...
  86. ncbi request reprint Role of endothelium in hyperemia during cortical spreading depression (CSD) in the rat
    Katsuyoshi Shimizu
    Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston Salem, NC 27157 1083, USA
    Brain Res 928:40-9. 2002
    ..Thus, our results provide strong evidence that endothelium-mediated mechanisms have minimal effects on the CSD-associated hyperemia...

Research Grants3

  1. VASCULAR RESPONSES DURING CORTICAL SPREADING DEPRESSION
    David Busija; Fiscal Year: 2001
    ....
  2. IMPAIRED CORONARY ARTERY FUNCTION IN INSULIN RESISTANCE
    David Busija; Fiscal Year: 2003
    ..Findings from this project may provide important information that can be used in future studies to design treatments to prevent or abort the cardiovascular complications of insulin resistance. ..
  3. Cerebrovascular Dysfunction in Insulin Resistance
    David Busija; Fiscal Year: 2004
    ..We believe that our studies will result in new and important findings that will lead to improved therapies to reduce morbidity and mortality in IR individuals. ..