Central mineralocorticoid receptor blockade improves volume regulation andreduces sympathetic drive in heart failure

The mineralocorticoid (MC) receptor antagonist spironolactone (SL) improves morbidity and mortality in patients with congestive heart failure (CHF). W e tested the hypothesis that the central nervous system actions of SL contr ibute to its beneficial effects. SL (100 ng/h for 28 days) or ethanol vehic le (VEH) was administered intracerebroventricularly or intraperitoneally to rats with CHF induced by coronary artery ligation (CL) and to SHAM-operate d controls. The intracerebroventricular SL treatment prevented the increase in sodium appetite and the decreases in sodium and water excretion observe d within a week of CL in VEH-treated CHF rats. Intraperitoneal SL also impr oved volume regulation in the CHF rats, but only after 3 wk of treatment. F our weeks of SL treatment, either intracerebroventricularly or intraperiton eally, ameliorated both the increase in sympathetic drive and the impaired baroreflex function observed in VEH-treated CHF rats. These findings sugges t that activation of MC receptors in the central nervous system plays a cri tical role in the altered volume regulation and augmented sympathetic drive that characterize clinical heart failure.