ACUTE HYPOXIC PULMONARY VASOCONSTRICTION IN MAN IS ATTENUATED BY TYPE-I ANGIOTENSIN-II RECEPTOR BLOCKADE

Objectives: We examined the hypothesis that angiotensin II (ANG II) is a modulator of acute hypoxic pulmonary vasoconstriction (HPV) by look ing at the effect of losartan, a selective type 1 ANG II receptor anta gonist, on acute HPV in man. Methods: Ten normal volunteers were studi ed on two separate days. They either received pre-treatment with losar tan 25, 50, 100, 100 mg respectively on four consecutive days or match ed placebo. They were then rendered hypoxaemic, by breathing an N-2/O- 2 mixture for 20 min to achieve an SaO(2) of 85-90% adjusted for a fur ther 20 min to achieve an SaO(2) of 75-80%. Pulsed wave Doppler echoca rdiography was used to measure mean pulmonary artery pressure (MPAP), cardiac output and hence pulmonary vascular resistance (PVR). Results: Baseline MPAP and PVR (during normoxaemia) were unaffected by losarta n pre-treatment compared with placebo. However, losartan significantly ; reduced MPAP at both levels of hypoxaemia compared with placebo: 14. 7 +/- 0.7 vs 19.0 +/- 0.7 mmHg at an SaO(2) 85-90% (P < 0.01) and 20.0 +/- 0.7 vs 25.7 +/- 0.8 mmHg at an SaO(2) 75-80% (P < 0.05) respectiv ely. Similarly losartan significantly reduced PVR compared to placebo: 191 +/- 9 vs 246 +/- 10 dyne . s . cm(-5) at an SaO(2) 85-90% (P < 0. 005) and 233 +/- 12 vs 293 +/- 18 dyne . s . cm(-5) at an SaO(2) 75-80 % (P < 0.05), respectively. Pre-treatment with losartan, however, had no significant effect on systemic vascular resistance although losarta n compared to placebo resulted in a significant (P < 0.05) reduction i n mean arterial pressure at an SaO(2) 75-80%: 78 +/- 2 vs 87 +/- 2 mmH g. Conclusions: Losartan had no effect on baseline pulmonary haemodyna mics but significantly attenuated acute hypoxic pulmonary vasoconstric tion, suggesting that angiotensin II plays a role in modulating this r esponse in man via its effects on the type 1 angiotensin II receptor.