Lisinopril attenuates acute hypoxic pulmonary vasoconstriction in humans

Objective: We have studied the effects of angiotensin-converting enzyme (ACE) inhibition with lisinopril on acute hypoxic pulmonary vasoconstriction (HPV). Design: Randomized, double-blind, placebo-controlled study in ten healthy volunteers. Subjects received four daily doses of lisinopril or matched placebo before attending the laboratory 5 h after taking the final dose. After reaching a resting hemodynamic state, subjects were made hypoxemic (SaO(2), 75 to 80%) for 30 min. Measurements: Pulmonary and systemic hemodynamic parameters were measured noninvasively at baseline and after 30 min of hypoxemia. Results: Mean pulmonary artery pressure (MPAP) and total pulmonary vascular resistance (TPR) were similar at baseline on both study days. The increase in MPAP induced by hypoxemia was significantly blunted by pretreatment with lisinopril (means and 95% confidence interval [CI] for difference) 13.4 mm Hg vs placebo 19.6 mm Hg (95% CI, 2.5, 9.9). Likewise, the TPR response to hypoxemia was significantly blunted by lisinopril: 124 dyne . s . cm(-5) vs placebo 179 dyne . s . cm(-5) (95% CI, 11, 99). Lisinopril had no confounding systemic effects on mean arterial pressure, cardiac output, or systemic vascular resistance at baseline or in response to hypoxemia. Conclusions: Lisinopril therefore significantly attenuated the pulmonary presser response to hypoxemia without decreasing baseline MPAP or TPR. This suggests that angiotensin II might play a modulatory role during HPV in man and that ACE inhibition may be a useful adjunctive treatment in hypoxemic pulmonary hypertension.