Endothelium-derived vascular relaxing factor

Forstermann, U., Goppelt-Strube, M., Frolich, J. C., and Busse, R. (1986). Inhibitors of acylcoenzyme A Lysolecithin acyltransferase activate the production of endothelium-derived vascular relaxing factor. J. Pharmacol. Exp. Ther. 238, 352-359. 

Griffith, T., Edwards, DH, Lewis, MJ, Newby, AC, and Henderson, AH. 1984. The nature of endothelium-derived vascular relaxant factor. Nature 308 645-647. 

Gryglewski RJ, Palmer RM, Moncada S. Superoxide anion is involved in the breakdown of endothelium-derived vascular relaxing factor. Nature 1986 320 454-456. 

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... 

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... 

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. 

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. 

Furchgott, R. F. (1988). Studies on relaxation of rabbit aorta by sodium nitrite The basis for the proposal that the acid-activatable factor from bovine retractor penis is inorganic nitrite and the endothelium-derived relaxing factor is nitric oxide. In Vasodilatation Vascular Smooth Muscle, Peptides, Autonomic Nerves, and Endothelium (P. M. Vanhoutte, ed.), pp. 401-414. Raven, New York. 

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.)... 

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