Endothelium-Derived Relaxing Factor (EDRF)
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Recent investigations have greatly improved our understanding of the chemical nature of endothelium-derived relaxing factor (EDRF) and the regulation and metabolic pathway of its production. EDRF is a potent but labile relaxing factor with a biologic half-life of between 6.3 and 50 seconds in an oxygenated aqueous medium.1,2 The production of EDRF from the endothelium requires an increase in intracellular calcium.3,6 Following its production and release from the endothelial cell, EDRF is transferred to the vascular smooth muscle (VSM) where it activates soluble guanylate cyclase resulting in an increase in smooth muscle cyclic GMP concentration, which correlates with its relaxing action.7–13 Extremes of both high and low oxygen tension inhibit the production or stability of EDRF.14–15 Early investigations into the chemical nature of EDRF implicated an unstable, non-prostanoid oxidation product of arachidonic acid or some type of free radical.1,16–18 A great deal of recent evidence, however, suggests that EDRF is nitric oxide or a similar nitrogen oxide species.19–29 EDRF can be formed from L-arginine by a pathway involving a calcium-, calmodulin-and NADPH-dependent enzyme.30–39 EDRF synthesis has now been described in a wide range of cell types in addition to the endothelium, and indeed EDRF may be the second messenger responsible for the activation of guanylate cyclase in most cells containing the enzyme.34,35,38–43 This manuscript will present data from our laboratory which support these and other pharmacologic characteristics of EDRF.
KeywordsNitric Oxide Sodium Nitroprusside Soluble Guanylate Cyclase Branch Pulmonary Artery Microcarrier Bead
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