Blockade of renal effects of dopamine in the dog by the DA1 antagonist SCH 23390

Abstract

Dopamine (DA) acts on two receptor subtypes, DA1 and DA2. The purpose of this study was to determine which subtype is involved in the increments in renal blood flow (RBF) and electrolyte excretion produced by DA. Mongrel dogs were anesthetized with pentobarbital sodium. Phenoxybenzamine (10 mg X kg-1 ia) and propranolol (5 mg X kg-1 iv) were administered to exclude effects mediated by alpha- and beta-adrenoceptors. DA was infused into the renal artery before and after administration of either the selective DA1 antagonist SCH 23390 or the selective DA2 antagonist domperidone. With DA alone, RBF increased by 52 +/- 7%, Na+ excretion increased by 35 +/- 8%, and K+ excretion increased by 35 +/- 5%. Infusion of SCH 23390 (0.5 micrograms X kg-1 X min-1) completely blocked DA-induced increase in RBF and electrolyte excretion. Intravenous infusion of domperidone (1 microgram X kg-1 X min-1) did not attenuate the responses to DA. Neither SCH 23390 nor domperidone affected base-line RBF or electrolyte excretion, suggesting that in these experiments endogenous DA was not active. In conclusion, these data indicate that the effects of DA to increase RBF and electrolyte excretion are the result of action on DA1 receptors.