Haemodynamic and endocrine effects of type 1 angiotensin II receptor blockade in patients with hypoxaemic cor pulmonale

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Abstract
Objectives: Angiotensin II (ANG II) is known to be a potent vasoconstrictor agent in the pulmonary circulation. Furthermore, type 1 ANG II receptor blockade with losartan attenuates acute hypoxic pulmonary vasoconstriction in normal subjects. The aim of this study was therefore to evaluate the haemodynamic and endocrine sequelae of type 1 ANG II receptor blockade in patients with hypoxaemic cor pulmonale. Methods: Nine patients with chronic obstructive pulmonary disease (COPD) age 67 ± 3 years with pulmonary hypertension and normal left ventricular systolic function were studied on two separate occasions in a double-blind, placebo-controlled, crossover study. They were randomised to receive either 50 mg of oral losartan or matched placebo. Pulsed wave Doppler echocardiography was used to measure cardiac output (CO), mean pulmonary artery pressure (MPAP) and hence systemic vascular resistance (SVR) and total pulmonary vascular resistance (TPR). Haemodynamic measurements and venous blood samples were taken at baseline and after 2 and 4 h. Results: Maximal effects were observed at 4 h where losartan compared to placebo resulted in a significant reduction in both MPAP (28.6 ± 2.0 vs 32.4 ± 1.5 mmHg) and TPR (428 ± 40 vs 510 ± 40 dyn·s·cm−5), respectively. Similarly losartan compared to placebo resulted in a significant reduction in MAP (87 ± 4.5 vs 93 ± 3.2 mmHg) and SVR (1293 ± 94 vs 1462 ± 112 dyn·s·cm−5), and significantly increased CO (5.58 ± 0.43 vs 5.31 ± 0.42 l/min). In addition, plasma aldosterone was significantly lower after treatment with losartan compared to placebo: 76 ± 23 vs 164 ± 43 pg/ml respectively. Conclusions: Thus, selective type 1 ANG II receptor blockade appears to have beneficial pulmonary and endocrine effects, suggesting a possible therapeutic role in the management of hypoxaemic cor pulmonale.

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