Hypertension, Vol 12, 365-372, Copyright © 1988 by American Heart Association
S Moncada, RM Palmer and EA Higgs
Endothelium-derived relaxing factor (EDRF) is a labile humoral agent
released by vascular endothelium that mediates the relaxation induced by
some vasodilators, including acetylcholine and bradykinin. EDRF also
inhibits platelet aggregation, induces disaggregation of aggregated
platelets, and inhibits platelet adhesion to vascular endothelium. These
actions of EDRF are mediated through stimulation of the soluble guanylate
cyclase and the consequent elevation of cyclic guanosine
3',5'-monophosphate. EDRF has been identified as nitric oxide (NO). The
pharmacology of NO and EDRF is indistinguishable; furthermore, sufficient
NO is released from endothelial cells to account for the biological
activities of EDRF. Organic nitrates exert their vasodilator activity
following conversion to NO in vascular smooth muscle cells. Thus, NO may be
considered the endogenous nitrovasodilator. NO is synthesized by vascular
endothelium from the terminal guanido nitrogen atom(s) of the amino acid
L-arginine. This indicates the existence of an enzymic pathway in which
L-arginine is the endogenous precursor for the synthesis of NO. The
discovery of the release of NO by vascular endothelial cells, the
biosynthetic pathway leading to its generation, and its interaction with
other vasoactive substances opens up new avenues for research into the
physiology and pathophysiology of the vessel wall.
ARTICLES
The discovery of nitric oxide as the endogenous nitrovasodilator
Wellcome Research Laboratories, Beckenham, Kent, United Kingdom.
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