Cardiac Hypertrophy in Copper-Deficient Rats Is Not Attenuated by Angiotensin II Receptor Antagonist L-158,809

Abstract

We tested the hypothesis that cardiac hypertrophy which accompanies copper (Cu) deficiency was mediated by angiotensin II (Ang II). Thirty 17-day-old male Holtzman rats were offered a semipurified low-Cu diet (0.45 mg Cu/kg) for 39 days. Fifteen controls (Cu adequate) were given supplemental Cu (20 microgram/ml) in their drinking water, the other 15 (Cu deficient) were given deionized water. Five from each dietary treatment group were chronically infused by using osmotic pumps for 4 weeks with the Ang II receptor antagonist L-158,809, and five from each group were infused with propylene glycol vehicle. Five from each group were not implanted. Blood pressure (BP) changes to injection of Ang II, phenylephrine, and acetylcholine were monitored in cannulated rats. Cu-deficient rats had higher heart weight, left ventricular (LV)/body weight (BW), right ventricular (RV)/BW, lower mean BP, and coronary vascular resistance (CVR) than Cu-adequate rats. L-158-809 did not alter Cu levels or RV/BW in either dietary group, but did lower LV/BW, CVR, and mean BP in both dietary groups. Since Ang II blockage lowered HW/BW and LV/BW in both groups, the stimulus for cardiac hypertrophy in Cu-deficient rats remains unknown.