Plasma endothelin levels: a meaningless number?

Endothelin (ET)-1 is a potent vasoactive peptide which is mostly secreted toward the vessel wall and the circulatory levels of which are quite low; for these reasons changes in plasma ET-1 may be difficult to detect even after the application of strong stimuli, which, in theory, should profoundly alter its production. We have examined the effects of a number of such stimuli and found that in humans the only one which consistently increased plasma ET-1 was the exposure to hypobaric hypoxia; moreover under these circumstances the increments in plasma ET-1 were correlated with the changes in pulmonary systolic pressure, suggesting a role of circulating ET-1 in the adaptation of pulmonary vessels to high altitude. In contrast no consistent changes of ET-1 were observed in response to sympathetic activation induced either by exposure to cold, standing, reduction in blood pressure and blood withdrawal. In response to angioplasty of renal artery stenosis a concomitant reduction in plasma ET-1 and angiotensin II (AngII) was observed in patients 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.