CEREBRAL VESSEL INNERVATION IN HYPERTENSION

Summary

Principal Investigator: TONY J LEE
Affiliation: Southern Illinois University School of Medicine
Country: USA
Abstract: Strong evidence has indicated that cerebral blood vessels from several species receive nonadrenergic, noncholinergic (NANC) vasodilator nerves. The nature of their transmitter substances, however, has not been positively determined. Several neural peptides such as vasoactive intestinal polypeptide (VIP), calcitonin gene-related peptide (CGRP) and peptide histidine isoleucine (PHI) are present in high concentrations in cerebral arteries. These peptides induce an endothelium-independent vasodilation which is associated with an enhanced vascular cAMP formation, and therefore have been suggested to be the potential transmitters for cerebral vasodilation. Thus, multiple transmitters from different sources appear to mediate the cerebral neurogenic vasodilation. This possibility is further supported by our recent findings that transmural nerve stimulation (TNS)-induced but also cGMP content. Activation of the soluble guanylate cyclase, however, plays a predominant role in the neurogenic vasodilation. The candidate transmitter for activating the cGMP pathway and its relationship with the neuronal peptides in cerebral neurogenic vasodilation remains unknown. the endothelium-mediated dilations in cerebral and peripheral blood vessels are well established. There is good evidence that the endothelium-derived relaxing factor (EDRF) is nitric oxide (NO) or a NO-releasing substance, and that the precursor from which it is synthesized is L-arginine. EDRF or NO induces vasodilation by activating soluble guanylate cyclase, and its synthesis is blocked by arginine analogues. In isolated cerebral arteries, we have demonstrated that the TNS-induced vasodilation was nearly abolished by a potent NO synthesis inhibitor. The inhibition was completely reversed by L-arginine but no D-arginine. It is hypothesized that NO or a NO- releasing substance mediates a major component of the NANC neurogenic vasodilation in the cerebral artery. The exact transmission mechanism of this dilator factor/NO has not been delineated. The proposed study continues to characterize the transmitter mechanism in cerebral NANC vasodilation. The in vitro tissue bath techniques, and techniques of biochemical and chemical analysis and morphology (immunohistochemistry) will be utilized to provide a comprehensive and multi-faceted approach to the problem. We plan to 1) examine formations of cyclic nucleotide and cyclic nucleotide protein kinase activities in isolated cerebral arteries without endothelial cells upon TNS, and applications of NO and vasodilating neural peptides (VIP, GCRP and PHI); 2) characterize the dilator responses in isolated cerebral arteries induced by TNS, and applications of NO and vasodilating peptides, and 3) examine the possibility that NO involved in cerebral neurogenic vasodilation can originate in the smooth muscle and the perivascular nerves. This research is a step toward our long-term goal to define the transmitter mechanisms in cerebral vasodilation and constriction, and their alterations in cerebral vascular diseases.
Funding Period: 1981-09-01 - 1995-06-30
more information: NIH RePORT

Top Publications

  1. ncbi Statins prevent beta-amyloid inhibition of sympathetic alpha7-nAChR-mediated nitrergic neurogenic dilation in porcine basilar arteries
    Min-Liang Si
    Department of Pharmacology, Southern Illinois University School of Medicine, Springfield, IL 62794-9629, USA
    J Cereb Blood Flow Metab 25:1573-85. 2005
  2. ncbi Cholinesterase inhibitor blockade and its prevention by statins of sympathetic alpha7-nAChR-mediated cerebral nitrergic neurogenic vasodilation
    Mansoor Mozayan
    Department of Pharmacology, Southern Illinois University School of Medicine, Springfield, Illinois62794-9629, USA
    J Cereb Blood Flow Metab 26:1562-76. 2006
  3. ncbi Monoamine uptake inhibitors block alpha7-nAChR-mediated cerebral nitrergic neurogenic vasodilation
    Cheng Long
    Department of Pharmacology, School of Medicine, Southern Illinois University, Springfield, Illinois, USA
    Am J Physiol Heart Circ Physiol 291:H202-9. 2006
  4. ncbi Statins prevent cholinesterase inhibitor blockade of sympathetic alpha7-nAChR-mediated currents in rat superior cervical ganglion neurons
    Mansoor Mozayan
    Department of Pharmacology, Southern Illinois University School of Medicine, PO Box 19629 Springfield, IL 62794 9629, USA
    Am J Physiol Heart Circ Physiol 293:H1737-44. 2007
  5. ncbi Presynaptic prostaglandin E2 EP1-receptor facilitation of cerebral nitrergic neurogenic vasodilation
    Vikram Jadhav
    College of Life Sciences, Tzu Chi University, 701 Sec 3, Chung Yang Road, Hualien, Taiwan
    Stroke 40:261-9. 2009
  6. ncbi Endogenous methyl palmitate modulates nicotinic receptor-mediated transmission in the superior cervical ganglion
    Hung Wen Lin
    Department of Pharmacology, Southern Illinois University School of Medicine, Springfield, IL 62702, USA
    Proc Natl Acad Sci U S A 105:19526-31. 2008

Detail Information

Publications6

  1. ncbi Statins prevent beta-amyloid inhibition of sympathetic alpha7-nAChR-mediated nitrergic neurogenic dilation in porcine basilar arteries
    Min-Liang Si
    Department of Pharmacology, Southern Illinois University School of Medicine, Springfield, IL 62794-9629, USA
    J Cereb Blood Flow Metab 25:1573-85. 2005
    ..Statins may offer an alternative strategy in the prevention and treatment of AD...
  2. ncbi Cholinesterase inhibitor blockade and its prevention by statins of sympathetic alpha7-nAChR-mediated cerebral nitrergic neurogenic vasodilation
    Mansoor Mozayan
    Department of Pharmacology, Southern Illinois University School of Medicine, Springfield, Illinois62794-9629, USA
    J Cereb Blood Flow Metab 26:1562-76. 2006
    ..The efficacy of ChEIs may be improved by concurrent use of statins...
  3. ncbi Monoamine uptake inhibitors block alpha7-nAChR-mediated cerebral nitrergic neurogenic vasodilation
    Cheng Long
    Department of Pharmacology, School of Medicine, Southern Illinois University, Springfield, Illinois, USA
    Am J Physiol Heart Circ Physiol 291:H202-9. 2006
    ..These results further support the hypothesis of axo-axonal interaction in nitrergic regulation of cerebral vascular tone...
  4. ncbi Statins prevent cholinesterase inhibitor blockade of sympathetic alpha7-nAChR-mediated currents in rat superior cervical ganglion neurons
    Mansoor Mozayan
    Department of Pharmacology, Southern Illinois University School of Medicine, PO Box 19629 Springfield, IL 62794 9629, USA
    Am J Physiol Heart Circ Physiol 293:H1737-44. 2007
    ..Protection of alpha7-nAChR function from ChEI inhibition by concurrent administration of statins may provide an alternative strategy in improving the efficacy of AD and VaD therapy...
  5. ncbi Presynaptic prostaglandin E2 EP1-receptor facilitation of cerebral nitrergic neurogenic vasodilation
    Vikram Jadhav
    College of Life Sciences, Tzu Chi University, 701 Sec 3, Chung Yang Road, Hualien, Taiwan
    Stroke 40:261-9. 2009
    ..We investigated the role of endogenous PGE(2) and its presynaptic EP(1) receptor subtype in modulating the autonomic neurotransmission in cerebral vasculature...
  6. ncbi Endogenous methyl palmitate modulates nicotinic receptor-mediated transmission in the superior cervical ganglion
    Hung Wen Lin
    Department of Pharmacology, Southern Illinois University School of Medicine, Springfield, IL 62702, USA
    Proc Natl Acad Sci U S A 105:19526-31. 2008
    ..Endogenous PAME appears to play a role in modulation of the autonomic ganglionic transmission and to complement the vasodilator effect of NO...