[Roles of vasoactive factors synthetized by endothelium in pulmonary arterial hypertension].
Pulmonary vascular endothelium synthesizes and releases two groups of vasoactive substances, namely the endothelium-derived relaxing and contracting factors. Among the former, the effects of nitric oxide (NO), formerly known as endothelium-derived relaxing factor (EDRF), and those of the so-called endothelium-derived hyperpolarizing factor (EDHF) have been extensively investigated. Among the latter, endothelin is probably one of the most potent endogenous vasoconstrictors. NO is a free radical which can be readly inactivated by hemoglobin. NO has all the characteristics of a gas, whereas its pharmacological properties are consistent with those of an endogenous nitrovasodilator. Therefore, inhalation of the gas NO is now considered as one of the most promising means to treat persistent pulmonary hypertension of the newborn. EDHF relaxes vascular smooth muscle through activation of ATP-dependent potassium channels. Both the chemical nature and the physiological role of EDHF are still unclear. The pharmacological properties of endothelin are far from being unequivocal. It is a potent vasoconstrictor, when it directly acts on vascular smooth muscle. However, it can also induce the release of NO and EDHF, hence causing vasorelaxation. These effects of endothelin are mediated by various transduction pathways. Activations of ET-B receptors located on endothelium on the one hand, and ET-A receptors located on smooth muscle on the other hand, are responsible for relaxation and constriction of vascular smooth muscle, respectively. Such highly complex cellular mechanisms highlight the need for further insight into the physiology of the cell related to the pulmonary circulation. This, in turn, will help to better define the target upon which one can try to correct the abnormal function of the cell underlying the pathophysiological processes.
Lévy
M
M
Laboratoire de Physiologie Respiratoire, Faculté de Médecine Cochin-Port-Royal, Université Paris V, France.
Sabry
S
S
Mercier
J C
JC
Dinh-Xuan
A T
AT
D001685:Biological Factors / Q000378:metabolism; D016232:Endothelins / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000503:physiopathology; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy / Q000503:physiopathology*; D008168:Lung / Q000098:blood supply; D009569:Nitric Oxide / Q000378:metabolism*; D014665:Vasodilator Agents / Q000378:metabolism*
D001685:Biological Factors; D016232:Endothelins; D014665:Vasodilator Agents; C067410:endothelium-dependent hyperpolarization factor; D009569:Nitric Oxide