ET-1 infusion increases systemic vascular resistance and depresses cardiacoutput in patients with chronic hypoxaemia and pulmonary hypertension

The pulmonary vascular effects of the endothelium-derived peptide endotheli n (ET) vary depending on the existing vascular tone, modes of administratio n and species studied; ET can cause both pulmonary vasodilatation and vasoc onstriction. Increased plasma levels of ET have been reported in hypoxic pu lmonary hypertension, although it is unclear whether ET is a mediator or a marker of hypoxia-induced increase in pulmonary vascular resistance (PVR). In our study, the plasma levels of ET-1 and the functional effects of ET-1 infusion in patients (n = 4) with chronic hypoxaemia and elevated PVR were evaluated. At rest, the arterial and venous ET-1-levels (13 +/- 2 and 12 +/ - 1 fmol/ml, respectively) were significantly higher than those detected in venous plasma of an age-matched healthy control group (7 +/- 1 fmol/ml). C onsecutive 10 min infusions of ET-1 at 1, 5, 10 and 15 ng/kg/min into the p ulmonary artery decreased cardiac output (by 32%) and stroke volume (by 33% ) and increased the systemic vascular resistance (by 62%) and arteriovenous oxygen difference (by 83%) at the highest dose. No deleterious effect was observed in the pulmonary circulation. The present study therefore suggests that intra-pulmonarily administered ET does not attenuate the increased PV R associated with chronic hypoxaemia.