[Nitric oxide and circulatory homeostasis].

In 1980, Furchgott and Zawadski demonstrated that arterial smooth muscle cell relaxation in response to acetylcholine was dependent on the anatomical integrity of the endothelium. They baptized the principle responsible for this intercellular relationship EDRF (Endothelium Derived Relaxing Factor). EDRF was identified 7 years later to be a gaseous free radical: nitric oxide (NO). Many substances, such as bradykinin, histamine, serotonin, acetylcholine and exert their vasodilator effect by stimulating the endothelial production of NO. However, the most powerful stimulus of NO production by the endothelium is currently considered to be the shearing forces of the blood on the endothelium. The vasodilatation produced in response to an increased blood flow (flow-dependent vasodilatation) is therefore added to the local vasodilatation of metabolic origin. NO can therefore be considered to be an "endogenous nitrate", generated locally by the endothelium and exerting an essentially paracrine action (relaxation of adjacent smooth muscle cells, but also inhibition of platelet aggregation). Many clinical studies have demonstrated the existence of abnormalities of endothelium-dependent vasodilatation in atherosclerosis. While acetylcholine infusion induces vasodilatation in a healthy coronary artery it induces vasoconstriction in an atherosclerotic coronary artery. While a reduction of NO generation and/or its activity could be an important element of the physiology of atherosclerosis, excess NO production is largely responsible for the hypotension of septic shock.