NITRIC OXIDE SYNTHASE IN THE JUXTAGLOMERULAR APPARATUS

Summary

Principal Investigator: Christopher S Wilcox
Abstract: DESCRIPTION (provided by applicant): We have found that endothelial dysfunction develops early in human hypertension and chronic kidney disease (CKD). It is accompanied by increased reactive oxygen species (ROS) which can inactivate nitric oxide (NO). However, there is also an increase in asymmetric dimethylarginine (ADMA) which can inhibit NOS. Plasma levels of ADMA and markers of ROS predict cardiovascular disease and CKD progression. ADMA is generated intracellularly by protein arginine methyltransferases (PRMTs), metabolized by dimethylarginine dimethylaminohydrolases (DDAHs) and exported by cationic amino acid transporters (CATs). The hypothesis is that ROS, generated within preglomerular vascular smooth muscle cells (PGVSMCs), renal glomerular endothelial cells (RGECs) and renal proximal tubule cells (RPTCs) enhance intracellular ADMA which reduces vascular NO generation and angiogenesis and reduces absolute proximal reabsorption (APR). Therefore, this hypothesis links these two major risk factors. The first aim will contrast cell stably transfected with p22phox (S-p22phox) with empty vector wild type cells (Wt). We will study the effects of superoxide (O2.-) vs. H2O2 on the activities and expression of the enzymes and transporters that regulate intracellular ADMA in these three cell types. We will test our hypothesis that PGVSMCs generate a "myocyte derived endothelial regulator factor" driven by NADPH oxidase that signals to adjacent ECs to reduce NO activity and prevent proliferation and angiogenesis via ADMA and/or H2O2. This is a novel pathway in the vessel wall to compliment endothelium to VSMC communication. Similar studies in S-p22phox PTCs will probe the role of ADMA in the impaired 22Na+ uptake and O2 usage. We have found profound reductions in APR in the SHR model of oxidative stress that are dependent on p22phox, ROS and DDAH-1. A reduced Na+ reabsorption by the energy-efficient proximal tubule dictates enhanced delivery and reabsorption by downstream nephron segments. This could account for the decreased efficiency of O2 usage and the hypoxia of kidneys from animals with oxidative stress. Therefore, Aim 2 will investigate these interactions in vivo. We will study these effects on the NHE inhibitory protein-2 (NHERF-2) in vivo in the microperfused proximal tubules of WKY and SHR, by the addition of drugs to the perfusates, or use of small interference RNAs targeting NHERF-2 or specific proteins involved in production, metabolism and transport of ADMA and ROS and in vascular function in mice transgenic for p22phox in VSMCs. These studies are an escalating series of mechanistic studies in cells and functional studies in the kidney and vessels to test the hypothesis that ADMA mediates the effects of ROS on blood vessels and proximal tubular transport which could lead to new targets for intervention to prevent progressive cardiovascular and kidney diseases.
Funding Period: 1997-07-01 - 2015-06-30
more information: NIH RePORT

Top Publications

  1. ncbi Acute antihypertensive action of nitroxides in the spontaneously hypertensive rat
    Kinjal Patel
    Georgetown University, Division of Nephrology and Hypertension, 3800 Reservoir Rd, NW, PHC F6003, Washington, DC 20007, USA
    Am J Physiol Regul Integr Comp Physiol 290:R37-43. 2006
  2. pmc Effects of tempol and redox-cycling nitroxides in models of oxidative stress
    Christopher S Wilcox
    Division of Nephrology and Hypertension, Department of Medicine and Center for Hypertension, Kidney and Vascular Health, Georgetown University, Washington, DC, United States
    Pharmacol Ther 126:119-45. 2010
  3. pmc Myogenic responses of mouse isolated perfused renal afferent arterioles: effects of salt intake and reduced renal mass
    En Yin Lai
    Division of Nephrology and Hypertension, Georgetown University Medical Center, Washington, DC 20007, USA
    Hypertension 55:983-9. 2010
  4. pmc Adenosine A(2) receptors modulate tubuloglomerular feedback
    Mattias Carlström
    Department of Medicine, Georgetown University Medical Center, Washington, District of Columbia, USA
    Am J Physiol Renal Physiol 299:F412-7. 2010
  5. pmc Angiotensin II and NADPH oxidase increase ADMA in vascular smooth muscle cells
    Zaiming Luo
    Division of Nephrology and Hypertension, Georgetown University Medical Center, 6 PHC, Suite F6003, 3800 Reservoir Rd, NW, Washington DC 20007, USA
    Hypertension 56:498-504. 2010
  6. pmc Impaired endothelial function and microvascular asymmetrical dimethylarginine in angiotensin II-infused rats: effects of tempol
    Dan Wang
    Division of Nephrology and Hypertension, Georgetown University, Washington, DC, USA
    Hypertension 56:950-5. 2010
  7. pmc Superoxide dismutase 1 limits renal microvascular remodeling and attenuates arteriole and blood pressure responses to angiotensin II via modulation of nitric oxide bioavailability
    Mattias Carlström
    Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden
    Hypertension 56:907-13. 2010
  8. pmc Adenosine A2A receptor activation attenuates tubuloglomerular feedback responses by stimulation of endothelial nitric oxide synthase
    Mattias Carlström
    Division of Nephrology and Hypertension, and Hypertension, Kidney and Vascular Research Center, Georgetown University, Washington, DC 20057, USA
    Am J Physiol Renal Physiol 300:F457-64. 2011
  9. pmc Superoxide modulates myogenic contractions of mouse afferent arterioles
    En Yin Lai
    Division of Nephrology and Hypertension, Georgetown University, Washington, DC 20007, USA
    Hypertension 58:650-6. 2011
  10. pmc An overview of candesartan in clinical practice
    Zeeshan Khawaja
    Division of Nephrology and Hypertension, Georgetown University Medical Center, 3800 Reservoir Road, Washington, DC, USA
    Expert Rev Cardiovasc Ther 9:975-82. 2011

Research Grants

  1. Novel Mechanisms and Therapies in Heart Failure
    Howard A Rockman; Fiscal Year: 2013
  2. Mechanisms of Microvascular Control and Coordination in Health and Disease
    Gerald A Meininger; Fiscal Year: 2013
  3. Neurohumoral control of veins in hypertension
    Gregory D Fink; Fiscal Year: 2013
  4. IPF Fibroblast Phenotype
    Craig A Henke; Fiscal Year: 2013
  5. HORMONAL REGULATION OF BLOOD PRESSURE
    Michal Laniado Schwartzman; Fiscal Year: 2013
  6. Signaling Processes Underlying Cardiovascular Function
    Jeffrey Robbins; Fiscal Year: 2013
  7. OXIDATIVE STRESS IN THE KIDNEY IN HYPERTENSION
    Christopher S Wilcox; Fiscal Year: 2013
  8. Ether Lipids, Elcosanoids, and Lung Cell Pathophysiology
    CHRISTINA CARROLL LESLIE; Fiscal Year: 2013
  9. Protein-glycan Interactions in the Vascular System
    Lijun Xia; Fiscal Year: 2013
  10. Regulatory Mechanisms In Intestinal Motility
    Kenton M Sanders; Fiscal Year: 2013

Detail Information

Publications39

  1. ncbi Acute antihypertensive action of nitroxides in the spontaneously hypertensive rat
    Kinjal Patel
    Georgetown University, Division of Nephrology and Hypertension, 3800 Reservoir Rd, NW, PHC F6003, Washington, DC 20007, USA
    Am J Physiol Regul Integr Comp Physiol 290:R37-43. 2006
    ..SOD exerts a delayed hypotensive action that is not enhanced by liposome encapsulation, suggesting it must diffuse to an extravascular site...
  2. pmc Effects of tempol and redox-cycling nitroxides in models of oxidative stress
    Christopher S Wilcox
    Division of Nephrology and Hypertension, Department of Medicine and Center for Hypertension, Kidney and Vascular Health, Georgetown University, Washington, DC, United States
    Pharmacol Ther 126:119-45. 2010
    ..Indeed, tempol given from birth prolonged the life span of normal mice. However, presently tempol has been used only in human subjects as a topical agent to prevent radiation-induced alopecia...
  3. pmc Myogenic responses of mouse isolated perfused renal afferent arterioles: effects of salt intake and reduced renal mass
    En Yin Lai
    Division of Nephrology and Hypertension, Georgetown University Medical Center, Washington, DC 20007, USA
    Hypertension 55:983-9. 2010
    ..This myogenic response is impaired substantially in the mouse model of prolonged reduced renal mass, especially during high salt intake...
  4. pmc Adenosine A(2) receptors modulate tubuloglomerular feedback
    Mattias Carlström
    Department of Medicine, Georgetown University Medical Center, Washington, District of Columbia, USA
    Am J Physiol Renal Physiol 299:F412-7. 2010
    ..Simultaneous application of A(1) and A(2) antagonists abolished the TGF response (DeltaP(SF): 0.4 +/- 0.3 mmHg). In conclusion, adenosine A(2) receptors modulate the TGF response by counteracting the effects of adenosine A(1) receptors...
  5. pmc Angiotensin II and NADPH oxidase increase ADMA in vascular smooth muscle cells
    Zaiming Luo
    Division of Nephrology and Hypertension, Georgetown University Medical Center, 6 PHC, Suite F6003, 3800 Reservoir Rd, NW, Washington DC 20007, USA
    Hypertension 56:498-504. 2010
    ..This could underlie increases in cellular asymmetrical dimethylarginine during oxidative stress...
  6. pmc Impaired endothelial function and microvascular asymmetrical dimethylarginine in angiotensin II-infused rats: effects of tempol
    Dan Wang
    Division of Nephrology and Hypertension, Georgetown University, Washington, DC, USA
    Hypertension 56:950-5. 2010
    ..These effects were dependent on reactive oxygen species and could, therefore, be targeted with effective antioxidant therapy...
  7. pmc Superoxide dismutase 1 limits renal microvascular remodeling and attenuates arteriole and blood pressure responses to angiotensin II via modulation of nitric oxide bioavailability
    Mattias Carlström
    Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden
    Hypertension 56:907-13. 2010
    ..This may prevent an early and exaggerated blood pressure response to angiotensin II...
  8. pmc Adenosine A2A receptor activation attenuates tubuloglomerular feedback responses by stimulation of endothelial nitric oxide synthase
    Mattias Carlström
    Division of Nephrology and Hypertension, and Hypertension, Kidney and Vascular Research Center, Georgetown University, Washington, DC 20057, USA
    Am J Physiol Renal Physiol 300:F457-64. 2011
    ..In conclusion, adenosine A(2A) receptor activation attenuated TGF responses by stimulation of endothelial NOS (eNOS), presumably in the afferent arteriole. Moreover, NO derived from both eNOS and nNOS in the JGA may blunt TGF responses...
  9. pmc Superoxide modulates myogenic contractions of mouse afferent arterioles
    En Yin Lai
    Division of Nephrology and Hypertension, Georgetown University, Washington, DC 20007, USA
    Hypertension 58:650-6. 2011
    ....
  10. pmc An overview of candesartan in clinical practice
    Zeeshan Khawaja
    Division of Nephrology and Hypertension, Georgetown University Medical Center, 3800 Reservoir Road, Washington, DC, USA
    Expert Rev Cardiovasc Ther 9:975-82. 2011
    ..In this article, we review the literature for the role of candesartan-based therapy for hypertension, stroke, diabetes mellitus and heart failure...
  11. ncbi Towards developing new strategies to reduce the adverse side-effects of nonsteroidal anti-inflammatory drugs
    Noritaka Kawada
    Department of Nephrology, Osaka University Graduate School of Medicine, 2 2 Yamadaoka, Suita, Osaka, 565 0871, Japan
    Clin Exp Nephrol 16:25-9. 2012
    ....
  12. pmc p47(phox) is required for afferent arteriolar contractile responses to angiotensin II and perfusion pressure in mice
    En Yin Lai
    Hypertension, Kidney, and Vascular Research Center, Georgetown University Medical Center, NW, Washington, DC 20007, USA
    Hypertension 59:415-20. 2012
    ..These effects likely contribute to hypertension and renal vasoconstriction during infusion of angiotensin II...
  13. pmc Asymmetric dimethylarginine and reactive oxygen species: unwelcome twin visitors to the cardiovascular and kidney disease tables
    Christopher S Wilcox
    Division of Nephrology and Hypertension, Georgetown University Medical Center, 3800 Reservoir Rd, NW, 6 PHC Building, F6003, Washington, DC 20007, USA
    Hypertension 59:375-81. 2012
    ..Thus, we conclude that reactive oxygen species and asymmetric dimethylarginine form a tightly coupled amplification system that translates cardiovascular/kidney risk into overt disease...
  14. pmc Effects of the antioxidant drug tempol on renal oxygenation in mice with reduced renal mass
    En Yin Lai
    Division of Nephrology and Hypertension, Center for Hypertension, Kidney and Vascular Research, Georgetown University, Washington, DC, USA
    Am J Physiol Renal Physiol 303:F64-74. 2012
    ..Thus hypoxia in RRM may be the outcome of NADPH oxidase-initiated ROS generation, leading to mitochondrial uncoupling counteracted by defense pathways coordinated by Nrf-2...
  15. pmc Acute knockdown of uncoupling protein-2 increases uncoupling via the adenine nucleotide transporter and decreases oxidative stress in diabetic kidneys
    Malou Friederich-Persson
    Division of Integrative Physiology, Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden
    PLoS ONE 7:e39635. 2012
    ..However, blockade of the diabetes-induced upregulation of UCP- 2 results in excessive uncoupling and reduced oxidative stress in the kidney via activation of ANT...
  16. pmc Kidney function after in vivo gene silencing of uncoupling protein-2 in streptozotocin-induced diabetic rats
    Malou Friederich Persson
    Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden
    Adv Exp Med Biol 765:217-23. 2013
    ..The reason for the lack of effect of reducing UCP-2 is presently unknown but may involve compensatory mitochondrial uncoupling by the adenosine nucleotide transporter...
  17. pmc Renal oxygenation and function of the rat kidney: effects of inspired oxygen and preglomerular oxygen shunting
    Christopher S Wilcox
    Kidney and Vascular Research Center, Georgetown University Hypertension, Washington, DC 20007, USA
    Adv Exp Med Biol 765:329-34. 2013
    ..Thus, the preglomerular diffusional shunt appeared to stabilize intrarenal PO(2) during changes in arterial oxygen and to protect NO signaling within the kidney...
  18. pmc Renal afferent arteriolar and tubuloglomerular feedback reactivity in mice with conditional deletions of adenosine 1 receptors
    Lingli Li
    National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 10 Center Drive MSC 1370, Bethesda, MD 20892, USA
    Am J Physiol Renal Physiol 303:F1166-75. 2012
    ..A1AR on AA smooth muscle cells are primarily responsible for TGF activation, but A1AR on extravascular cells, perhaps mesangial cells, appear to contribute to the TGF response...
  19. pmc Blood pressure, blood flow, and oxygenation in the clipped kidney of chronic 2-kidney, 1-clip rats: effects of tempol and Angiotensin blockade
    Fredrik Palm
    Division of Nephrology and Hypertension, Hypertension, Kidney, and Vascular Center, and Angiogenesis Program of the Lombardi Cancer Center, Georgetown University, Washington, DC 20007, USA
    Hypertension 55:298-304. 2010
    ..In conclusion, acute administration of Tempol is more effective than candesartan in reducing the mean arterial blood pressure and improving renal blood perfusion and oxygenation in the clipped kidney of chronic 2K,1C rats...
  20. pmc Enhanced tubuloglomerular feedback in mice with vascular overexpression of A1 adenosine receptors
    Mona Oppermann
    National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA
    Am J Physiol Renal Physiol 297:F1256-64. 2009
    ..These data indicate that A1AR expression in vascular smooth muscle cells is a critical component for TGF signaling and that changes in renal vascular A1AR expression may determine the magnitude of TGF responses...
  21. pmc Cellular ADMA: regulation and action
    Tom Teerlink
    Department of Clinical Chemistry, VU University Medical Center, Amsterdam, The Netherlands
    Pharmacol Res 60:448-60. 2009
    ..An understanding of this important balance requires knowledge of these three processes that regulate the intracellular levels of ADMA and arginine...
  22. ncbi Angiotensin II infusion alters vascular function in mouse resistance vessels: roles of O and endothelium
    Dan Wang
    Division of Nephrology and Hypertension, Department of Medicine, Georgetown University, Washington, DC 20007, USA
    J Vasc Res 43:109-19. 2006
    ..2 and ONOO- in the vascular smooth muscle cell...
  23. ncbi Oxidative stress and nitric oxide in kidney function
    Magali Araujo
    Division of Nephrology and Hypertension, Georgetown University, 4000 Reservoir Road, Washington, DC 20057, USA
    Curr Opin Nephrol Hypertens 15:72-7. 2006
    ..The purpose of this review is to highlight the recent studies on oxidative stress and nitric oxide in the kidney, focusing on their interaction in normal and pathological conditions...
  24. ncbi RNA silencing in vivo reveals role of p22phox in rat angiotensin slow pressor response
    Paul Modlinger
    Division of Nephrology and Hypertension, Georgetown University, Washington, DC, USA
    Hypertension 47:238-44. 2006
    ..005). An increase in p22phox is required for increased renal NADPH oxidase activity, expression of Nox proteins and oxidative stress, and contributes < or =50% to hypertension during an Ang II slow-pressor response...
  25. ncbi NADPH oxidases in the kidney
    Pritmohinder S Gill
    Angiogenesis Section, Lombardi Cancer Center, Cardiovascular Kidney Institute and Division of Nephrology and Hypertension, Georgetown University, Washington, District of Columbia 20007, USA
    Antioxid Redox Signal 8:1597-607. 2006
    ..Experimental studies of the distribution, signaling, and function of NADPH oxidases in the kidney are described...
  26. ncbi Role of extracellular superoxide dismutase in the mouse angiotensin slow pressor response
    William J Welch
    Cardiovascular Kidney Institute and Division of Nephrology and Hypertension, Georgetown University, Washington, DC, USA
    Hypertension 48:934-41. 2006
    ....
  27. ncbi beta(1) Receptors protect the renal afferent arteriole of angiotensin-infused rabbits from norepinephrine-induced oxidative stress
    Dan Wang
    Division of Nephrology and Hypertension and the Cardiovascular Kidney Institute, Georgetown University Medical Center, Washington, DC 20007, USA
    J Am Soc Nephrol 17:3347-54. 2006
    ..Aff have robust alpha(1)-receptor contraction and beta(1)-receptor dilation. NE elicits beta(1) signaling via cAMP that moderates oxidative stress and contractions in Aff from AngII-infused rabbits...
  28. ncbi Hydrogen peroxide mediates a transient vasorelaxation with tempol during oxidative stress
    Yifan Chen
    Cardiovascular Kidney Hypertension Institute, Division of Nephrology and Hypertension, Georgetown Univ, 4000 Reservoir Road, NW, Bldg D 399, Washington, DC 20057, USA
    Am J Physiol Heart Circ Physiol 293:H2085-92. 2007
    ....
  29. ncbi Isoform-specific regulation by N(G),N(G)-dimethylarginine dimethylaminohydrolase of rat serum asymmetric dimethylarginine and vascular endothelium-derived relaxing factor/NO
    Dan Wang
    Division of Nephrology and Hypertension, Georgetown University, Washington, DC 20007, USA
    Circ Res 101:627-35. 2007
    ..This implies specific functions of DDAH isoforms...
  30. ncbi Roles of vasoconstrictor prostaglandins, COX-1 and -2, and AT1, AT2, and TP receptors in a rat model of early 2K,1C hypertension
    William J Welch
    Division of Nephrology and Hypertension, Georgetown University, Washington, DC 20007, USA
    Am J Physiol Heart Circ Physiol 293:H2644-9. 2007
    ..2K,1C hypertension in rats activates renin, O(2)*(-), and vasoconstrictor PGs. Hypertension is maintained by AT(1)Rs and by COX-1, but not COX-2, products that activate TPRs...
  31. ncbi Expression of NG,NG-dimethylarginine dimethylaminohydrolase and protein arginine N-methyltransferase isoforms in diabetic rat kidney: effects of angiotensin II receptor blockers
    Maristela L Onozato
    Division of Nephrology and Endocrinology, University of Tokyo, Tokyo, Japan
    Diabetes 57:172-80. 2008
    ..We tested the hypothesis that increased serum ADMA (S(ADMA)) in the streptozotocin (STZ)-induced diabetic rat model of diabetes is mediated by an angiotensin receptor blocker-sensitive change in DDAH or PRMT expression...
  32. ncbi Dimethylarginine dimethylaminohydrolase (DDAH): expression, regulation, and function in the cardiovascular and renal systems
    Fredrik Palm
    Division of Nephrology and Hypertension, Georgetown University, 3800 Reservoir Road N W, Washington, DC 20007, USA
    Am J Physiol Heart Circ Physiol 293:H3227-45. 2007
    ....
  33. ncbi Acute antihypertensive action of Tempol in the spontaneously hypertensive rat
    Xueguang Chen
    Division of Nephrology and Hypertension, Georgetown University, 3800 Reservoir Road N W, Washington, DC 20007, USA
    Am J Physiol Heart Circ Physiol 293:H3246-53. 2007
    ..The acute antihypertensive action of Tempol depends on the independent effects of potentiation of nitric oxide and inhibition of the peripheral SNS that involves the activation of K(ATP) channels...
  34. ncbi Angiotensin II type 2 receptors and nitric oxide sustain oxygenation in the clipped kidney of early Goldblatt hypertensive rats
    Fredrik Palm
    Division of Nephrology and Hypertension, Cardiovascular Kidney Hypertension Institute, Georgetown University, 3800 Reservoir Rd, NW, PHC F6003, Washington, DC 20007, USA
    Hypertension 51:345-51. 2008
    ..This discloses a novel mechanism whereby angiotensin can prevent hypoxia in a kidney challenged with a reduced perfusion pressure...
  35. ncbi Asymmetric dimethylarginine and lipid peroxidation products in early autosomal dominant polycystic kidney disease
    Dan Wang
    Cardiovascular Kidney Hypertension Institute, Division of Nephrology and Hypertension and Angiogenesis Section, Lombardi Cancer Institute, Georgetown University, Washington, DC 20007, USA
    Am J Kidney Dis 51:184-91. 2008
    ....
  36. pmc Asymmetric dimethylarginine, oxidative stress, and vascular nitric oxide synthase in essential hypertension
    Dan Wang
    Georgetown University Hypertension, Kidney and Vascular Disorders Center, Division of Nephrology and Hypertension, Georgetown University, Washington, DC 20007 USA
    Am J Physiol Regul Integr Comp Physiol 296:R195-200. 2009
    ..In conclusion, elevated levels of ADMA and oxidative stress in a group of hypertensive patients could contribute to the associated microvascular endothelial dysfunction and elevated blood pressure...
  37. pmc Chemistry and antihypertensive effects of tempol and other nitroxides
    Christopher S Wilcox
    Division of Nephrology and Hypertension, Kidney and Vascular Disorder Center, Georgetown University, Washington, DC 20007, USA
    Pharmacol Rev 60:418-69. 2008
    ..Thus, tempol is broadly effective in reducing blood pressure, whether given by acute intravenous injection or by prolonged administration, in a wide range of rodent models of hypertension...
  38. pmc Comparison of inhibitors of superoxide generation in vascular smooth muscle cells
    Z Luo
    Hypertension, Kidney and Vascular Centre, Georgetown University, Washington, DC 20007, USA
    Br J Pharmacol 157:935-43. 2009
    ....
  39. pmc Endothelial dysfunction and enhanced contractility in microvessels from ovariectomized rats: roles of oxidative stress and perivascular adipose tissue
    Dan Wang
    Division of Nephrology and Hypertension, Georgetown University Medical Center, 6 PHC, Suite F6003, 3800 Reservoir Rd NW, Washington, DC 20007
    Hypertension 63:1063-9. 2014
    ....

Research Grants30

  1. Novel Mechanisms and Therapies in Heart Failure
    Howard A Rockman; Fiscal Year: 2013
    ..The results will be used to define novel strategies for manipulation of these recently discovered mechanisms for the therapy of patients with heart failure. ..
  2. Mechanisms of Microvascular Control and Coordination in Health and Disease
    Gerald A Meininger; Fiscal Year: 2013
    ..End of Abstract) ..
  3. Neurohumoral control of veins in hypertension
    Gregory D Fink; Fiscal Year: 2013
    ..This project tests the idea that altered structure or function of veins also may cause hypertension, and that it may be possible to treat hypertension using drugs that affect veins. ..
  4. IPF Fibroblast Phenotype
    Craig A Henke; Fiscal Year: 2013
    ..A major objective of this Program Project is to inform decisions of the IPF Clinical Network by providing information that can be translated into novel therapeutic strategies for IPF. ..
  5. HORMONAL REGULATION OF BLOOD PRESSURE
    Michal Laniado Schwartzman; Fiscal Year: 2013
    ..ular tone, in the pathophysiology of hypertension and cardiovascular disease. ..
  6. Signaling Processes Underlying Cardiovascular Function
    Jeffrey Robbins; Fiscal Year: 2013
    ..These projects are supported by 3 Cores: Core A: The Administrative Core;Core B: The Physiology Core and Core C: The Imaging-Cell Culture Core. (End of Abstract) ..
  7. OXIDATIVE STRESS IN THE KIDNEY IN HYPERTENSION
    Christopher S Wilcox; Fiscal Year: 2013
    ..These are supported by the Administrative, Animal and Bioanalytical Cores. ..
  8. Ether Lipids, Elcosanoids, and Lung Cell Pathophysiology
    CHRISTINA CARROLL LESLIE; Fiscal Year: 2013
    ..By using multidisciplinary approaches, we will determine the structural identity of lipid mediators, the molecular mechanisms involved in their production and how they function to regulate lung responses. ..
  9. Protein-glycan Interactions in the Vascular System
    Lijun Xia; Fiscal Year: 2013
    ..This information may suggest new approaches to treat heart attacks, strokes, and other cardiovascular disorders. ..
  10. Regulatory Mechanisms In Intestinal Motility
    Kenton M Sanders; Fiscal Year: 2013
    ..The investigative team is highly synergistic and collaborative, and the PPG has a long track-record of productivity and novel discovery ..
  11. Interactive Signaling Modules in Vascular Inflammation
    Linda H Shapiro; Fiscal Year: 2013
    ..abstract_text> ..
  12. Structural bases of the functions of RNA-protein machines
    THOMAS ARTHUR STEITZ; Fiscal Year: 2013
    ..Also of interest will be the ways in which the structures and properties of RNA molecules can be utilized to carry out various biological functions often analogous to those performed by proteins. ..
  13. Autocoids in Hypertension: Pathogenesis and End Organ Damage
    Oscar A Carretero; Fiscal Year: 2013
    ..Te PPG provides integration of our efforts, collaboration, sharing of ideas and expertise, thus accelerating acquisition of knowledge on the causes of hypertension and EOD. (End of Abstract) ..
  14. DEVELOPMENT AND CONTROL OF PULMONARY ALVEOLAR STABILITY
    Samuel Hawgood; Fiscal Year: 2013
    ..abstract_text> ..
  15. CARDIOVASCULAR DYNAMICS AND THEIR CONTROL
    John E Hall; Fiscal Year: 2013
    ..End of Abstract) ..
  16. RAGE and Mechanisms of Vascular Dysfunction
    Shi Fang Yan; Fiscal Year: 2013
    ..Using novel and state-of-the-art techniques, floxed mice and molecular approaches to gene regulation, we are well-positioned to lead the study of RAGE in the next cycle of this Program. ..