Endothelium derived relaxing factor

Furchgott and Zawadzki [1] first discovered that endothelial cells release a substance(s) responsible for the relaxation of vascular smooth muscle by acetylcholine this substance was named endothelium-derived relaxing factor (EDRF). This epoch-making discovery answers the question raised for nearly one hundred years by pharmacologists about why vascular smooth muscle is relaxed by acetylcholine, which however elicits contraction of the other smooth muscles. Because of its instability, the true chemical nature of EDRF was not easily identified. Several years later, several research groups independently found that the biological activities and biochemical properties of EDRF were identical... 

Endothelium-derived relaxing factor (nitric oxide)... 

The results of a number of studies demonstrate that the gas nitric oxide (NO) plays a functional role in the central nervous system. This all originated with the discovery that the so-called endothelium-derived relaxing factor (EDRF), found in blood vessels, and thought to be a peptide, was in fact NO. The potential roles of this freely diffusible gas have subsequently been extended to many other tissues and organs but we will concentrate on the possible neuronal roles of what is obviously a novel mediator. There are also suggestions that the closely related carbon monoxide may also have a function in the central nervous system. 

Ignarro, L.J. (1990). Biosynthesis and metabolism of endothelium-derived relaxation factor. Ann. Rev. Pharmacol. Toxicol. 30, 535-560. 

Moncada, S., Radomski, M.W. and Palmer, R.M. (1988). Endothelium-derived relaxing factor identification as nitric oxide and role in the control of vascular tone and platelet function. Biochem. Pharmacol. 37, 2495-2501. 

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... 

Gryglewski, R.J., Palmer, R.M.J. and Moncada, S. (1986). Superoxide anion is involved in the breakdown of endothelium-derived relaxing factor. Nature 320, 454—456. 

ED35 Eflective dose producing 35% maximum response EDso Effective dose producing 50% maximum response EDF Eosinophil differentiation 6ctor EDL Extensor digitorum longus EDN Eosinophil-derived neurotoxin EDRF Endothelium-derived relaxing factor... 

First described in the 1980s as "endothelium-derived relaxing factor," nitric oxide (NO) is a vasodilator believed to play a role in regulation of blood pressure under physiologic and pathophysiological conditions. For example, inhibition of NO synthesis under normal conditions and during septic shock results in a significant elevation of blood pressure. 

L.J. Ignarro, G.M. Buga, K.S. Wood, R.E. Byrns, and G. Chaudhuri, Endothelium-derived relaxing factor produced and released from artery and vein is nitric-oxide. Proc. Natl. Acad. Sci. U.S.A. 84, 9265-9269 (1987). 

T. Akaike, M. Yoshida,Y. Miyamoto, K. Sato, M. Kohno, K. Sasamoto, K. Miyazaki, S. Ueda, and H. Maeda, Antagonistic action of imidazolineoxyl N-oxides against endothelium-derived relaxing factor. NO through a radical reaction. Biochemistry 32, 827-832 (1993). 

EDRF endothelium-derived relaxing factor GPDH glycerol phosphate dehydrogenase... 

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 ...

Palmer, R. M., Ferrige,A. G., Moncada, S., Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor, Nature 327 (1987), p. 524-526... 

Garthwaite J., Charles, S. L., Chess-Williams, R., Endothelium-derived relaxing factor release on activation of NMDA receptors suggests role as intercellular messenger in the brain, Nature 336 (1988), p. 385-388... 

Duchenne muscular dystrophy dimethyl formamide 5,5-dimethyl-1 -pyrroline-1 -oxide deoxynucleic acid diphenylene iodonium endothelium-derived relaxing factor epidermal growth factor early growth phase response gene ethyleneglycol- bis- (p- aminoethyl)-N,N,N, N -tetraacetic acid... 

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