Effect of dopamine beta-hydroxylase inhibition on systemic hemodynamics in conscious, spontaneously hypertensive rats

The acute and chronic effects of a potent and selective dopamine beta-hydroxylase inhibitor, SK&F 102698 [1-(3,5-difluorobenzyl)imidazole-2-thiol], on systemic hemodynamic variables were assessed in chronically instrumented spontaneously hypertensive and normotensive Wistar rats. The changes observed in the hypertensive rats were compared with those obtained by vehicle in a different group of rats. Following intragastric administration of SK&F 102698 (75 mg/kg), blood pressure and cardiac output decreased gradually in both strains of rats, while total peripheral vascular resistance remained unchanged. The antihypertensive effect of repeated daily administration of SK&F 102698 in the hypertensive rats was sustained for the duration of treatment. During the acute phase, the decrease in cardiac output was due to bradycardia. In addition, as a result of hemodynamic changes, SK&F 102698 significantly reduced the minute work output of the heart. The results indicate that SK&F 102698 lowers blood pressure primarily by decreasing cardiac output.