Endothelin-releasing stimuli and calcium antagonists in normal and pathological conditions

Endothelin-1 is a potent vasoconstrictive peptide which circulates in blood at very low concentrations. It is mostly released from endothelial cells towards the vascular smooth muscle cells. Therefore studies addressed at increasing endothelin-1 production using physical stimuli may easily fail to cause sizeable modifications in plasma endothelin levels. Upright posture and exposure to cold, the two maneuvers so far most commonly used in humans, often have inconsistent effects on plasma endothelin-1.

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 pressure.

Hypobaric hypoxia appears to stimulate the secretion of endothelin-1 and this response may contribute to the adaptation by the systemic and pulmonary circulation to the stress of altitude. If this can be confirmed, calcium antagonists, which are known to antagonize endothelin-1 mediated vasoconstriction, may be used to alleviate the pulmonary hypertension that occasionally occurs under these specific circumstances.