Nitric oxide and NO-mimetic drugs

Nitric oxide, NO, is an endogenous, volatile and vasodilator molecule. Its discovery results from experiments which showed that the endothelium could release, under certain conditions, a vasodilator compound initially called, EDRF, “Endothelium-derived relaxing Factor”. For example, acetylcholine elicits relaxation of an isolated vessel when it is intact, but not when its endothelium is removed. This compound initially called EDRF is, in fact, nitric oxide, NO, and perhaps, in certain cases, a nitrosothiol like nitrosocysteine.

NO is the principal vasodilator factor released by endothelial cells. But a factor named EDHF (endothelium derived hyperpolarizing Factor) whose identity has not been perfectly defined could take part in the vasodilator effect by acting on potassium channels. Various molecules were supposed to be the EDHF, one of them is a polypeptide of 22 amino acid residues, perhaps CNP, C-type natriuretic peptide. There is no drug known to specifically modulate EDHF activity.  

NO was initially found in vascular endothelium. Endothelium is a monocellular layer, lining all the vascular tree, arteries and veins, from heart to capillaries, with an area of more than 1000 m2 . The endothelial cells, whose duration of life is estimated at 30 years, divide and migrate to cover damaged area. They can also create new capillary vessels: this process which is called angiogenesis plays an important part in tumoral growth. The vascular endothelium involves numerous types of receptors for acetylcholine, norepinephrine, serotonin, histamine and angiotensin; it also involves many enzymes, for example angiotensin converting enzyme, prostacyclin synthase, metalloproteases and NO-synthases.

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