Plasma endothelin levels: a meaningless number?

Endothelin (ET)-1 is a potent vasoactive peptide which is mostly secreted t oward the vessel wall and the circulatory levels of which are quite low; fo r these reasons changes in plasma ET-1 may be difficult to detect even afte r the application of strong stimuli, which, in theory, should profoundly al ter its production. We have examined the effects of a number of such stimul i and found that in humans the only one which consistently increased plasma ET-1 was the exposure to hypobaric hypoxia; moreover under these circumsta nces the increments in plasma ET-1 were correlated with the changes in pulm onary systolic pressure, suggesting a role of circulating ET-1 in the adapt ation of pulmonary vessels to high altitude. In contrast no consistent chan ges of ET-1 were observed in response to sympathetic activation induced eit her by exposure to cold, standing, reduction in blood pressure and blood wi thdrawal. In response to angioplasty of renal artery stenosis a concomitant reduction in plasma ET-1 and angiotensin II (AngII) was observed in patien ts who, prior to angioplasty, had a high degree of activation of the renin system, supporting the possibility that in these specific conditions AngII may actually stimulate ET-1 production in vivo.