Relaxation endothelial-derived relaxing factor

The literature on the role of hyperpolarization and endothelial-dependent relaxation is complex because there are at least two relaxing compounds released from the endothelium nitric oxide and endothelial-derived hyperpolarizing factor (EDHF). There are conflicting reports on the mechanism of action of each agent. ADP (Brayden, 1991) and acetylcholine (Feletau and Vanhoutte, 1988 Keef and Bowen, 1989) induce relaxation via the endothelium, releasing nitric oxide and/or EDHF (Brayden and Wellman, 1989 Nagao... 

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... 

Chin, J.H., Azhar, S. and Hoffman, B.B. (1992). Inactivation of endothelial derived relaxing factor by oxidized lipoproteins. 

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... 

EPA Eicosapentaenoic acid EpDIF Epithelial-derived inhibitory factor also known as epithelium/derived relaxant fector EPO Eosinophil peroxidase EPOR Erythropoietin receptor EPR Effector cell protease EPX Eosinophil protein X ER Endoplasmic reticulum ERCP Endoscopic retrograde cholangiopancreatography E-selectin Endothelial selectin formerly known as endothelial leucocyte adhesion molecule-1 (ELAM-1)... 

A. Wennmalm, B. Lanne, and A.S. Petersson, Detection of endothelial-derived relaxing factor in human plasma in die basal state and following ischemia using electron-paramagnetic resonance spectrometry. Anal. Biochem. 187, 359-363 (1990). 

In blood vessels, the relaxant action of ACh on muscle tone is indirect, because it involves stimulation of M3-cho-linoceptors on endothelial cells that respond by liberating NO (= endothelium-derived relaxing factor). The latter diffuses into the subjacent smooth musculature, where it causes a relaxation of active tonus (p. 121). 

Proposed mechanism by which nitroglycerin and the organic nitrates produce relaxation in vascular smooth muscle. Nitrates induce endothelial cells to release NO or a nitrosothiol (endothelium-derived releasing factor, or EDRF). EDRF activates the enzyme guanylate cyclase, which causes the generation of cyclic guanosine monophosphate (GMP), producing a decrease in cytosolic free calcium. The end result is vascular smooth muscle relaxation. SH, sulfhydryl. 

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. 

Mayer, B., Schmidt, K., Humbert, P., and Bohme, E. (1989). Biosynthesis of endothelium-derived relaxing factor A cytosolic enzyme in porcine aortic endothelial cells Ca -... 

Muscarinic agonists release endothelium-derived relaxing factor, identified as nitric oxide (NO), from the endothelial cells. The NO diffuses to adjacent vascular smooth muscle, where it activates guanylyl cyclase and increases cGMP, resulting in relaxation (see Figure 12-2). Isolated vessels prepared with the endothelium preserved consistently reproduce the... 

Activation of endothelial cell muscarinic receptors by acetylcholine (Ach) releases endothelium-derived relaxing factor (nitric oxide), which causes relaxation of vascular smooth muscle precontracted with norepinephrine, 10-8M. Removal of the endothelium by rubbing eliminates the relaxant effect and reveals contraction caused by direct action of Ach on vascular smooth muscle. (NA, noradrenaline [norepinephrine]. Numbers indicate the log concentration applied at the time indicated.)... 

The second indication came from studies of vascular regulation. Several molecules, such as acetylcholine, were known to cause relaxation of blood vessels. This effect occurred only when the vessels were prepared so that the luminal endothelial cells covering the smooth muscle of the vessel wall were retained. Subsequent studies showed that endothelial cells respond to these vasorelaxants by releasing a soluble endothelial-derived relaxing factor (EDRF). EDRF acts on vascular muscle to elicit relaxation. These findings prompted an intense search for the identity of EDRF. 

Endothelial cell-derived relaxing factor. See Nitric oxide, NO Endotoxins 431... 

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