Effect of domperidone on renal response to certain atrial natriuretic substances in rats

Anesthetized rats, maintained on an intravenous (1 ml/h) infusion of saline, were injected with either atrial extract from normal rats (AE), atriopeptin III (APIII, 24 amino acids) or atrial peptide (AP, 28 amino acids) as either a bolus injection (1 atrial equivalent of AE, 1 microgram APIII, or 1 microgram AP) or by constant infusion (1.7 ng APIII or AP/min for 30 min) in isotonic saline. Diuretic, natriuretic, and kaliuretic responses were determined by subtraction of baseline values from the renal response during the first 15 min after administration of the atrial natriuretic factor (ANF). The change in renal response observed in rats receiving saline and a bolus injection of an ANF was compared to the change in response observed in the same rats that received the dopaminergic antagonist, domperidone (0.2 microgram/kg, i.v.), and the same ANF. In the case of the renal response following infusion of an ANF, a paired comparison was made between domperidone-treated and untreated rats. Domperidone attenuated the renal response to AP, administered either as a bolus injection or a constant infusion, whereas domperidone significantly reduced renal response to APIII only following constant infusion. The renal response to a bolus injection of AE was not affected by the administration of domperidone. These findings suggest that the renal action of the putative circulating form of ANF, i.e. AP, is mediated via dopaminergic receptors, and that the route of administration may affect the mechanism of action of an ANF.