Renal I1-Imidazoline Receptor-Selective Compounds Mediate Natnuresis in the Rat

Abstract

In the present study, we investigated the renal actions of two compounds reported to interact with the imidazoline receptor: rilmenidine (I1-receptor selective, centrally acting antihypertensive) and agmatine (an endogenous clonidine-displacing substance). Rilmenidine (saline vehicle, 3 or 30 nmol/kg/min) or agmatine (saline vehicle, 3 or 30 nmol/kg/min) was infused directly into the renal artery of anesthetized (pentobarbitone) Sprague-Dawley rats (280-300 g) that had undergone a unilateral nephrectomy 7 to 10 days before the experiment. Rilmenidine produced an increase in urine flow rate at doses that failed to significantly alter blood pressure, creatinine clearance, or heart rate. The increase in urine flow rate was secondary to an increase in osmolar clearance, primarily composed of sodium. Free water clearance was not altered at these infusion rates. Agmatine also increased urine flow rate at doses that failed to alter blood pressure, creatinine clearance, and heart rate. The increase in urine flow rate was secondary to an increase in osmolar clearance, again primarily composed of sodium. The natriuretic action of rilmenidine and agmatine, at doses that do not lower blood pressure acutely, could be beneficial in the antihypertensive actions of these centrally acting agents.