ATTENUATION OF ADENYLATE CYCLASE-INDUCED INCREASES IN RENAL SODIUM-EXCRETION BY THE DOPAMINE-D-2 RECEPTOR AGONIST SK-AND-F-89124

1 Although the existence of D-2 receptor binding sites in kidney has b een identified, their functional significance in terms of influencing renal sodium excretion is not clear. In the present study we have exam ined the renal effects of a selective D-2 receptor agonist, SK&F 89124 , in anaesthetized rats. 2 Intravenous infusion of SK&F 89124 (0.3, 1 and 3 mu g kg(-1) min(-1) respectively) produced dose-dependent decrea ses in mean arterial blood pressure, heart rate and renal blood flow w ithout causing any significant changes in urine output, urinary sodium excretion, renal vascular resistance or glomerular filtration rate. T he changes in blood pressure, heart rate and renal blood flow caused b y SK&F 89124 were abolished by a selective D-2 receptor antagonist, do mperidone (50 mu g kg(-1) i.v. bolus; 10 mu g kg(-1) min(-1)). 3 Treat ment with 3-isobutyl-1-methylxanthine (IBMX, 1 mg kg(-1) bolus i.v.) o r forskolin (200 mu g kg(-1) bolus i.v.) produced increases in heart r ate, urine output and urinary sodium excretion, but there was no chang e in mean blood pressure. The natriuretic and diuretic response, but n ot tachycardiac response to IBMX or forskolin, was attenuated by SK&F 89124 (0.3 mu g kg(-1) min(-1)). 4 These results suggest that the sele ctive D-2 receptor agonist, SK&F 89124, produced a significant decreas e in blood pressure and heart rate via prejunctional D-2 receptor-medi ated inhibition of noradrenaline release from postganglionic sympathet ic nerve terminals. Although activation of renal tubular D-2 receptors had no significant effect on renal excretory function under basal con ditions, it is likely that these receptors may exert an opposing effec t on cAMP-mediated increases in renal sodium and water excretion.