Effect of Metoprolol Administration on Renal Sodium Handling in Experimental Congestive Heart Failure

Abstract

Background —Long-term metoprolol therapy improves cardiac performance and decreases mortality in patients with chronic congestive heart failure (CHF). This study examined the effect of long-term metoprolol therapy on renal sodium handling in an experimental rat model of CHF. Methods and Results —Rats with left coronary ligation and myocardial infarction–induced CHF were treated with metoprolol (1.5 mg · kg −1 · h −1 ) or vehicle for 3 weeks by osmotic minipump. They were then evaluated for their ability to excrete a short-term sodium load (5% body weight isotonic saline infusion over 30 minutes) and a long-term sodium load (change from low- to high-sodium diet over 8 days). All CHF rats had left ventricular end-diastolic pressure >10 mm Hg, and heart weight/body weight ratios averaged 0.68±0.02% (versus control of ≈0.40%). Compared with vehicle CHF rats (n=19), metoprolol CHF rats (n=18) had lower basal values of mean arterial pressure (122±3 versus 112±3 mm Hg) and heart rate (373±14 versus 315±9 bpm) and decreased heart rate responses to intravenous doses of isoproterenol. During short-term isotonic saline volume loading, metoprolol CHF rats excreted 54±4% more of the sodium load than vehicle CHF rats. During long-term dietary sodium loading, metoprolol CHF rats retained 28±3% less sodium than vehicle CHF rats. Conclusions —Metoprolol treatment of rats with CHF results in an improved ability to excrete both short- and long-term sodium loads.