(Hypertension. 1995;25:1202-1211.)
© 1995 American Heart Association, Inc.
Articles |
Nitric Oxide and Its Putative Role in Hypertension
From the Department of Medicine and Therapeutics, University of Glasgow (Scotland) (A.F.D.), and the Department of Physiology, University of Michigan, Ann Arbor (D.F.B.).
Correspondence to David F. Bohr, MD, Department of Physiology, University of Michigan, Ann Arbor, MI 48109-0622.
Key Words: nitric oxide • hypertension, arterial • arginine • endothelium-derived factors • vasodilator agents • nitro compounds • blood vessels
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Introduction |
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In the past 5 years, nitric oxide (NO) has become recognized as a major player in most physiological and pathophysiological processes. So much has been learned about the involvement of this molecule in these processes that it seems appropriate to survey the current state of this insight, with the goal of creating a solid foundation on which these studies can continue. In this review we deal first with the basic metabolism and actions of NO, emphasizing aspects of the subject that may have bearing on hypertension. We close with a review of studies that deal specifically with the involvement of NO in experimental and clinical hypertension. The involvement cannot now be clearly defined; however, this survey indicates that promising insights are within reach.
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Metabolism of NO |
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NO Synthase
NO synthase (NOS) is the ubiquitous enzyme that generates NO. Three isoenzymes have been described1 : isoform I, present in neuronal and epithelial cells; isoform II, first described in macrophages but now known to be present in other cells including vascular smooth muscle; and isoform III, the enzyme in endothelial cells that has received the most attention in connection with hypertension. These three isoenzymes have been purified and their cDNAs cloned. Isoform I is constitutively expressed in the brain, spinal cord, sympathetic ganglia, adrenal glands, and peripheral "nitroxidergic" nerves.2 3 4 It is calcium-calmodulin regulated. The gene for NOS isoform I has been localized recently to the 12q24.2
24.31 region of chromosome 12 by fluorescent in situ
hybridization.5 NOS isoform II can be induced in
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