Endothelium dependent relaxing factor

Three years later Robert F Furchgott discov ered that the relaxing of smooth muscles such as blood vessel walls was stimulated by an unknown substance produced in the lining of the blood vessels (the endothelium) He called this substance the endothelium-dependent relaxing factor or EDRF and in 1986 showed that EDRF was NO Louis J Ignarro reached the same conclusion at about the same time Further support was provided by Salvador Moncada who showed that endothelial cells did in deed produce NO and that the l arginine to l citrulline conversion was responsible... 

P2Y receptors that are found on endothelial cells elicit a Ca2+-dependent release of endothelium-dependent relaxing factor (EDRF) and vasodilation. A secondary activation of a Ca2+-sensitive phospholipase A2 increases the synthesis of endothelial prostacyclin, which limits the extent of intravascular platelet aggregation following vascular damage and platelet stimulation. The P2Y-mediated vasodilation opposes a vasoconstriction evoked by P2X receptors located on vascular smooth muscle cells. The latter elicit an endothelial-independent excitation (i.e. constriction). P2Y receptors are also found on adrenal chromaffin cells and platelets, where they modulate catecholamine release and aggregation respectively. 

Acetylcholine dilates all blood vessels causing flushing and fall in blood pressure. The vasodilatation is mediated through the release of endothelium dependent relaxing factor (EDRF). The fall in blood pressure is because of decrease in total peripheral resistance and cardiac output in anaesthetized animals. 

Gauthier KM, Edwards EM, Falck JR, Reddy DS, Campbell WB (2005) 14,15-epoxyeicosatrienoic acid represents a transferable endothelium-dependent relaxing factor in bovine coronary arteries. Hypertension 45 666-671... 

Increased formation and/or release of endothelium dependent relaxing factor (EDRF), i.e., NO (89). 

A relationship between polyol pathway activity and reduction in endothelium-dependent relaxation in aorta from chronic STZ-diabetic rats has recently been reported (Cameron and Cotter, 1992). In agreement with several previous studies (Oyama et al., 1986 Kamata et al., 1989), endothelial-dependent relaxation was defective in the diabetic rats but the deficit was prevented by prior treatment with an AR inhibitor. The mechanism underlying the defect has been speculated to be due to decreased production of endothelium-derived relaxing factor (EDRF) or nitric oxide, NO (Hattori et al., 1991). It has been speculated that these vascular abnormalities may lead to diminished blood flow in susceptible tissues and contribute to the development of some diabetic complications. NO is synthesized from the amino-acid L-arginine by a calcium-dependent NO synthase, which requires NADPH as a cofactor. Competition for NADPH from the polyol pathway would take place during times of sustained hyperglycaemia and... 

Fig. 9.1 Nitric oxide mediated inhibition of platelet activation. Abbreviations used NO, nitric oxide EDRF, endothelium-derived relaxing factor GC, guanylyl cyclase PDE, phosphodiesterase cGMP-PK, GMP-dependent protein kinase Raplb, small GTPase Raplb ...

Forstermann, U., Pollock, J. S., Schmidt, H. H. H. W., Heller, M., and Murad, F. (1991a). Calmodulin-dependent endothelium-derived relaxing factor/nitric oxide synthase activity is present in the particulate and cytosolic fractions of bovine aortic endothelial cells. Proc. Natl. Acad. Sci. U.S.A. 88, 1788-1792. 

Ignarro, L. J., Byms, R. E., Buga, G. M., Wood, K. S., and Chaudhuri, G. (1988b). Pharmacological evidence that endothelium-derived relaxing factor is nitric oxide Use of pyrogallol and superoxide dismutase to study endothelium-dependent and nitric oxide-elicited vascular smooth muscle relaxation, j. Pharmacol. Exp. Ther. 244, 181-189. 

Long, C. J., and Stone, T. W. (1985). The release of endothelium-derived relaxing factor is calcium-dependent. Blood Vessels 22, 205-208. 

Mayer, B., John, M., and Bohme, E. (1990b). Partial purification of a Ca /calmodulin-dependent endothelium-derived relaxing factor from porcine cerebellum. J. Cardiovasc. Pharmacol. 17, S46-S51. 

Mayer, B., Schmidt, K., Humbert, P. and Bohme, E. Biosynthesis of endothelium-derived relaxing factor a cytosolic enzyme in porcine aortic endothelial cells Ca2+-dependently converts L-arginine into an activator of soluble guanylyl cyclase, Biochem. Biophys. Research Commun. 1989, 164, 678-685. 

Knock GA, Mahn K, Mann GE, Ward JP, Aaronson PI. 2006. Dietary soy modulates endothelium-dependent relaxation in aged male rats Increased agonist-induced endothelium-derived hyperpolarising factor and basal nitric oxide activity. Free Radic Biol Med 41 731-739. 

Relaxation of blood vessels appears to be at least partially under the control of endothelial cells and their secreted products, especially endothelium-derived relaxation factor (EDRF). Oxidized LDL directly inhibits the endothelial cell-associated vessel relaxation. The generation of increased reactive oxygen species in association with elevated levels of blood cholesterol has also been reported. One of these reactive oxygen species, superoxide (O2), may interact with vasoactive EDRF (nitric oxide) locally in the artery wall, preventing endothelial cell-dependent vasodilation. In addition, a product of the reaction of nitric oxide and superoxide, the reactive peroxynitrite, may act to stimulate lipoprotein oxidation, which, as noted above, is regarded as an early step in atherosclerotic plaque generation. 

A role for endothelium-derived relaxing factor in renal vascular resistance and in glomerular and tubular function was first observed in the IPRK by Bhardwaj and Moore [198] and by Rademacher et al. [199-201]. Others have observed that manipulating nitric oxide can alter medullary oxygenation in the IPRK [109]. An increased endothelium-dependent vasodilator response to acetylcholine was observed in IPRK from cirrhotic rats [202]. Portal vein ligation also lowered renal vascular resistance that was not related to nitric oxide or prostaglandins, although increased nitric ox-... 

Bevan JA, Laher I Pressure and flow-dependent vascular tone. FASEB J. 5 2267-2273, 1991 Tolins JP, Palmer RM, Moncada S, Raij L Role of endothelium-derived relaxing factor in regulation of renal hemodynamic responses. Am.J. Physiol 258 H655-H662, 1990... 

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