EFFECTS OF ANGIOTENSIN-II RECEPTOR BLOCKADE ON HYPOXIA-INDUCED RIGHT-VENTRICULAR HYPERTROPHY IN RATS

It was the aim of the present study to characterize the hemodynamic, b iochemical and morphologic effect of angiotensin II receptor blockade on hypoxia-induced right ventricular hypertrophy in rats, Isolated rig ht ventricular hypertrophy was induced in female Sprague-Dawley rats b y intermittent hypoxia (IH; 10% O-2, 8h/ day, 5 days/week, 20 days of exposition, n=15). After completion of IH, left- (LV) and right-ventri cular (RV) hemodynamic parameters were measured under room air conditi ons in the intact, thiopental-anesthetized animals with special Millar ultraminiature tipcatheter-manometers. Cardiac output was determined using the thermodilution method, Cell volume (CV) of isolated cardiomy ocytes was measured with a Coulter Channellyzer after collagenase cell isolation. The specific activities of the myocardial pentose phosphat e pathway enzymes glucose-6-phosphate-dehydrogenase (G-6-PD) and 6-pho sphogluconate-dehydrogenase (6-PGD) were determined using a spectropho tometric assay. IH caused a rise in right ventricular systolic pressur e (RVSP) from 38.1 +/- 0.83 to 58.1 +/- 1.42 mmHg and an increase in t he RV weight/body weight ratio (RVW/BW) from 0.884 +/- 0.053 to 1.166 +/- 0.049 mg/g. The activities of G-6-PD and 6-PGD were significantly increased after IH in the RV, but not in the LV. CV was increased from 24 248 +/- 1193 to 29 541 +/- 1765 mu m(3), myocardial cell length wa s unchanged. IH had no influence on the LV parameters or cardiac outpu t. Co-infusion of the angiotensin II receptor antagonist losartan (LO; 12 mg/kg/d.i.p., n = 14) during the IH period reduced the rises in RV SP (49.4 +/- 2.06 mmHg), RVW/ BW (0.99 +/- 0.072 mg/g), G-6-PD and 6-P GD significantly, but not completely. The increase in CV, however, was prevented (24 524 +/- 2370 mu m(3)) entirely, We conclude from these data that the IH-induced RV-hypertrophy was primarily of the concentri c type, LO attenuated the hypoxia-induced isolated RV hypertrophy and significantly reduced the metabolic response of the RV. The LO effect was most potent with regard to the increase in cardiomyocyte volume. ( C) 1997 Academic Press Limited.