ANGIOTENSIN-II RECEPTOR BLOCKADE AND EFFECTS ON PULMONARY HEMODYNAMICS AND HYPOXIC PULMONARY VASOCONSTRICTION IN HUMANS

Study objective: We examined the hypothesis that angiotensin II (ANG I I) is a modulator of pulmonary vascular tone by examining the effects of ANG II blockade on pulmonary hemodynamics during normoxemia and hyp oxemia in normal volunteers with an activated renin angiotensin system (RAS). Participants and interventions: Eight normal volunteers, pretr eated with furosemide, were studied on two separate occasions and rece ived either an infusion of saralasin, 5 mu g/kg/min, ol placebo. After 20 min, they were rendered hypoxemic, by breathing N-2/O-2 mixture fo r 20 min to achieve arterial oxygen saturation (SaO(2)) of 85 to 90% a djusted for a further 20 min to achieve SaO(2) of 75 to 80%. Doppler e chocardiography was used to measure mean pulmonary artery pressure (MP AP), cardiac output, and hence total pulmonary vascular resistance (TP R). Results: Saralasin compared with placebo resulted in a significant (p<0.05) reduction in MPAP during normoxemia, 6.70+/-1.0 vs 11.7+/-1. 3 mm Hg; at SaO(2) of 85 to 90%, 14.7+/-1.4 vs 20.5+/-1.0 mm Hg; and a t SaO(2) of 75 to 80%, 18.1+/-1.9 vs 27.8+/-1.9 mm Hg, respectively. L ikewise saralasin compared with placebo resulted in a significant redu ction in TPR during normoxemia, 104+/-14 vs 180+/-20 dyne . s . cm(-5) ; at SaO(2) of 85 to 90%, 222+/-24 vs 295+/-21 dyne . s . cm(-5) and a t SaO(2) of 75 to 80%, 238+/-21 vs 362+/-11 dyne . s . cm(-5), respect ively. The Delta MPAP response to hypoxemia was likewise significantly (p<0.01) attenuated by saralasin infusion compared with placebo: mean difference 5.0 mm Hg, 95% confidence interval (CI) 1.9 to 8.08, and t here was a trend toward attenuation of the Delta TPR response to hypox emia (0.05<p<0.10): mean difference 47 dyne . s . cm(-5), 95% CI, -10 to 105. Conclusion: In addition to causing pulmonary vasodilatation in the presence of an activated RAS, our results suggest that ANG II rec eptor blockade attenuates acute hypoxic pulmonary vasoconstriction and that ANG II may play a role in modulating this response in normal man .