Angiotensin II Receptor Blockade and Effects on Pulmonary Hemodynamics and Hypoxic Pulmonary Vasoconstriction in Humans

¹ From the Department of Clinical Pharmacology, Ninewells Hospital and Medical School, University of Dundee, Dundee, Scotland

Study objective: We examined the hypothesis that angiotensin II (ANG II) is a modulator of pulmonary vascular tone by examining the effects of ANG II blockade on pulmonary hemodynamics during normoxemia and hypoxemia in normal volunteers with an activated renin angiotensin system (RAS).

Participants and interventions: Eight normal volunteers, pretreated with furosemide, were studied on two separate occasions and received either an infusion of saralasin, 5 µg/kg/min, or placebo. After 20 min, they were rendered hypoxemic, by breathing N₂/O₂ mixture for 20 min to achieve arterial oxygen saturation (SaO₂) of 85 to 90% adjusted for a further 20 min to achieve SaO₂ of 75 to 80%. Doppler echocardiography was used to measure mean pulmonary artery pressure (MPAP), cardiac output, and hence total pulmonary vascular resistance (TPR).

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 SaO₂ of 85 to 90%, 14.7±1.4 vs 20.5±1.0 mm Hg; and at SaO₂ of 75 to 80%, 18.1±1.9 vs 27.8±1.9 mm Hg, respectively. Likewise saralasin compared with placebo resulted in a significant reduction in TPR during normoxemia, 104±14 vs 180±20 dyne·s·cm⁵; at SaO₂ of 85 to 90%, 222±24 vs 295±21 dyne·s·cm⁵; and at SaO₂ of 75 to 80%, 238±21 vs 362±11 dyne·s·cm⁵, respectively. The 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 there was a trend toward attenuation of the TPR response to hypoxemia (0.05<p<0.10): mean difference 47 dyne·s·cm⁵, 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 receptor blockade attenuates acute hypoxic pulmonary vasoconstriction and that ANG II may play a role in modulating this response in normal man.

Key Words: angiotensin II blockade • hypoxemia • pulmonary circulation

Submitted on November 1, 1995
Accepted on April 10, 1996

This article has been cited by other articles:

				S. Patel, D.R. Woods, N.J. Macleod, A. Brown, K.R. Patel, H.E. Montgomery, and A.J. Peacock Angiotensin-converting enzyme genotype and the ventilatory responseto exertional hypoxia Eur. Respir. J., November 1, 2003; 22(5): 755 - 760. [Abstract] [Full Text] [PDF]

				R. Mathew, N. Y.-T. Fan, N. Yuan, P. N. Chander, M. H. Gewitz, and C. T. Stier Jr. Inhibition of NOS enhances pulmonary vascular changes in stroke-prone spontaneously hypertensive rats Am J Physiol Lung Cell Mol Physiol, January 1, 2000; 278(1): L81 - L89. [Abstract] [Full Text] [PDF]

				J.-M. Hyvelin, C. Guibert, R. Marthan, and J.-P. Savineau Cellular mechanisms and role of endothelin-1-induced calcium oscillations in pulmonary arterial myocytes Am J Physiol Lung Cell Mol Physiol, August 1, 1998; 275(2): L269 - L282. [Abstract] [Full Text] [PDF]