Mechanism of the depressor response to dopamine in the rat treated with phenoxybenzamine

Abstract

Alterations of hypotensive responses to dopamine by antagonists were characterized in alpha-blocked, anaesthetized rats. Responses were not affected by d-propranolol (0.1 mg/kg) whereas d,1-propranolol (0.1 mg/kg) or haloperidol (1.0 mg/kg) attenuated them; higher doses of inhibitors (1.0 mg/kg; 5.0 mg/kg, respectively) failed to produce a higher inhibition, but combinations of low doses abolished the depressor responses. In adrenalectomized rats, hypotensive responses decreased; haloperidol always attenuated the responses while d,1-propranolol became ineffective. Dopamine produced an enhancement of plasma adrenaline and noradrenaline levels, which was decreased by d,1-propranolol and increased by haloperidol. The data suggest that in rats the depressor component of dopamine is due to activation of both dopaminergic and beta-adrenoceptors. The beta component appears to be due to the release of adrenaline. The results also support the concept of the existence in sympathetic nerve endings and adrenal glands of stimulatory beta-adrenergic and inhibitory dopaminergic prejunctional receptors.