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Cardiovascular Research 1995 30(6):875-880; doi:10.1016/S0008-6363(95)00129-8
© 1995 by European Society of Cardiology
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Copyright © 1995, European Society of Cardiology

Acute hypoxic pulmonary vasoconstriction in man is attenuated by type I angiotensin II receptor blockade

David G. Kiely*, Robert I. Cargill and Brian J. Lipworth

Department of Clinical Pharmacology, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, UK

* Corresponding author. Tel. (+44-1382) 660111; Fax (+44-1382) 644972.

Objectives: We examined the hypothesis that angiotensin II (ANG II) is a modulator of acute hypoxic pulmonary vasoconstriction (HPV) by looking at the effect of losartan, a selective type 1 ANG II receptor antagonist, on acute HPV in man. Methods: Ten normal volunteers were studied on two separate days. They either received pre-treatment with losartan 25, 50, 100, 100 mg respectively on four consecutive days or matched placebo. They were then rendered hypoxaemic, by breathing an N2/O2 mixture for 20 min to achieve an SaO2 of 85–90% adjusted for a further 20 min to achieve an SaO2 of 75–80%. Pulsed wave Doppler echocardiography 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 losartan 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 SaO2 85–90% (P < 0.01) and 20.0 ± 0.7 vs 25.7 ± 0.8 mmHg at an SaO2 75–80% (P < 0.05) respectively. Similarly losartan significantly reduced PVR compared to placebo: 191 ± 9 vs 246 ± 10 dyne · s · cm–5 at an SaO2 85–90% (P < 0.005) and 233 ± 12 vs 293 ± 18 dyne · s · cm–5 at an SaO2 75–80% (P < 0.05), respectively. Pre-treatment with losartan, however, had no significant effect on systemic vascular resistance although losartan compared to placebo resulted in a significant (P < 0.05) reduction in mean arterial pressure at an SaO2 75–80%: 78 ± 2 vs 87 ± 2 mmHg. Conclusions: Losartan had no effect on baseline pulmonary haemodynamics but significantly attenuated acute hypoxic pulmonary vasoconstriction, suggesting that angiotensin II plays a role in modulating this response in man via its effects on the type 1 angiotensin II receptor.

KEYWORDS Hypoxia; Pulmonary artery; RAAS; Angiotensin II; Losartan


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D. G Kiely, R. I Cargill, N. M Wheeldon, W. J Coutie, and B. J Lipworth
Haemodynamic and endocrine effects of type 1 angiotensin II receptor blockade in patients with hypoxaemic cor pulmonale
Cardiovasc Res, January 1, 1997; 33(1): 201 - 208.
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