Prevention of cardiac hypertrophy by a sub-antihypertensive dose of the alpha 1-adrenergic antagonist bunazosin in Dahl salt-sensitive rats.
To assess the protective effect of an alpha 1-blocker on the development of cardiac hypertrophy, the selective alpha 1-receptor antagonist bunazosin (2 mg/kg/d, by oral gavage and in drinking water) was given to male Dahl salt-sensitive rats fed a 4% NaCl diet for 7 weeks. Control animals received water only by the same method. Treatment with bunazosin was started when the animals were 7 weeks of age. Blood pressure, pulse rates, and body weight were measured every week during the experiment. Urine was collected for 24 h on the final day of the experiment. All animals were killed by decapitation, blood was collected, and the heart was removed. In both the treated and control groups, time-dependent increase in blood pressure and body weight were observed, and there were no significant differences between the groups in blood pressure or body weight during the experiment. Pulse rate remained unchanged in both groups throughout the experiment. The left ventricular weight/body weight ratio and the left ventricular tissue DNA content were significantly lower in the rats receiving bunazosin than in the control rats. Plasma renin activity, plasma aldosterone, and plasma atrial natriuretic peptide did not differ significantly between the two groups. No significant differences in glomerular filtration rate, urine volume, sodium excretion, urinary metanephrine excretion, and urinary normetanephrine excretion were noted between the two groups. The results indicate that a sub-antihypertensive dose of bunazosin can inhibit the development of cardiac hypertrophy without suppression of the pressure load, suggesting an important role of alpha 1-adrenergic receptors in the pathogenesis of cardiac hypertrophy following the development of hypertension.