Highlights species and vascular bed differences in the release and mechanism of action of endothelial-derived relaxing factor.
Species- and bed-specific EDRF differences limit cross-model extrapolation; leaves open human venous endothelial mechanisms for targeted study.
The vascular endothelium is a source of a mediator of vascular smooth muscle (VSM) relaxation known as endothelial‐derived relaxing factor (EDRF). Endothelial‐dependent relaxation is dependent on the type of vessel under study (artery vs. vein) and on the vascular site from which the blood of vessels are derived. EDRF is released by bradykinin, adenosine, and adenosine triphosphate, substance P, serotonin, arachidonic acid, thrombin, and other relaxant substances. EDRF appears to be a labile substance with a six‐second half‐life that contains a labile ketone or carbonyl moiety in its active site. EDRF appears to be selectively inhibited by ouabain, pyruvate, and metabolic inhibitors and inactivated by potassium and sodium borohydride. EDRF appears to act by stimulating an increase in cyclic GMP in the smooth muscle cells of porcine tissues and possibly by other mechanisms in canine tissues. Canine veins possess receptors for porcine aortic EDRF but may not make EDRF itself or may have a different endothelial‐derived substance than canine arteries. Little is known concerning the factors that release or affect the action of EDRF, its mechanism of action or its chemical composition, especially in the pulmonary vasculature. The differences between release of EDRF from artery and vein and the responses to, and composition of, EDRF in vein and artery remain an area for further research.
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Greenberg et al. (1986) studied this question.
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