Aldosterone receptor blockade prevents the transition to cardiac pump dysfunction induced by beta-adrenoreceptor activation.

The transition from compensated to decompensated left ventricular hypertrophy (LVH) in hypertension involves excessive beta-adrenoreceptor (beta-AR) stimulation. To explore whether aldosterone receptor activation contributes toward beta-AR-induced left ventricular (LV) decompensation in hypertensive LVH, the effect of spironolactone (SPIRO; 80 mg x kg(-1) x day(-1)) on LV cavity dimensions, function, and chamber remodeling mechanisms was evaluated in spontaneously hypertensive rats (SHR) receiving a low dose of the beta-AR agonist isoproterenol (ISO) at 0.02 to 0.04 mg x kg(-1) . day for 4.5 months. ISO administered to SHR resulted in an increased 24-hour urinary aldosterone excretion and LV cavity dimensions, a right shift in LV diastolic pressure-volume relations, a decreased LV relative wall thickness, and increased total, noncross-linked, type I and type III myocardial collagen concentrations without further enhancing increased myocardial norepinephrine (NE) release. ISO reduced pump function without modifying intrinsic myocardial systolic function or inducing further myocyte necrosis or apoptosis. ISO only increased LV cavity volumes after prolonged periods of administration. SPIRO abolished ISO-induced chamber dilatation, wall thinning, and pump dysfunction and reduced total, noncross-linked, type I and type III myocardial collagen concentrations but failed to modify blood pressure, volume preloads, intrinsic myocardial systolic function, myocardial NE release, or the degree of necrosis or apoptosis. In conclusion, these results suggest that aldosterone receptor blockade, through load-independent effects, may be useful in preventing the transition from compensated LVH to dilatation and pump dysfunction mediated by chronic beta-AR activation.