HEMODYNAMIC AND ENDOCRINE EFFECTS OF TYPE-1 ANGIOTENSIN-II RECEPTOR BLOCKADE IN PATIENTS WITH HYPOXEMIC COR-PULMONALE

Objectives: Angiotensin II (ANG II) is known to be a potent vasoconstr ictor agent in the pulmonary circulation Furthermore, type I ANG II re ceptor blockade with losartan attenuates acute hypoxic pulmonary vasoc onstriction in normal subjects. The aim of this study was therefore to evaluate the haemodynamic and endocrine sequelae of type I ANG II rec eptor blockade in patients with hypoxaemic cor pulmonale. Methods: Nin e patients with chronic obstructive pulmonary disease (COPD) age 67 +/ - 3 years with pulmonary hypertension and normal left ventricular syst olic 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 (GO), mean pulmon ary artery pressure (MPAP) and hence systemic vascular resistance (SVR ) and total pulmonary vascular resistance (TPR). Haemodynamic measurem ents and venous blood samples were taken at baseline and after 2 and 4 h. Results: Maximal effects were observed at 4 h where losartan compa red 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 resu lted 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 significa ntly increased CO (5.58 +/- 0.43 vs 5.31 +/- 0.42 l/min). In addition, plasma aldosterone was significantly lower after treatment with losar tan compared to placebo: 76 +/- 23 vs 164 +/- 43 pg/ml respectively. C onclusions: Thus, selective type 1 ANG II receptor blockade appears to have beneficial pulmonary and endocrine effects, suggesting a possibl e therapeutic role in the management of hypoxaemic cor pulmonale.