ENDOTHELIN-RELEASING STIMULI AND CALCIUM-ANTAGONISTS IN NORMAL AND PATHOLOGICAL CONDITIONS

Background: Endothelin-1 is a potent vasoconstrictive peptide which ci rculates in blood at very low concentrations. It is mostly released fr om endothelial cells towards the vascular smooth muscle cells. Therefo re studies addressed at increasing endothelin-1 production using physi cal stimuli may easily fail to cause sizeable modifications in plasma endothelin levels. Upright posture and exposure to cold, the two maneu vers so far most commonly used in humans, often have inconsistent effe cts on plasma endothelin-1. Recent findings: In recent studies we have found that exposure to high altitude (4500-5000 m) caused, in normal subjects, significant increases in endothelin-1 which were correlated with those of mean arterial pressure and of systolic pulmonary pressur e. Conclusions: Hypobaric hypoxia appears to stimulate the secretion o f endothelin-1 and this response may contribute to the adaptation by t he systemic and pulmonary circulation to the stress of altitude. if th is can be confirmed, calcium antagonists, which are known to antagoniz e endothelin-1 mediated vasoconstriction, may be used to alleviate the pulmonary hypertension that occasionally occurs under these specific circumstances.