NATRIURESIS FOLLOWING CENTRAL AND PERIPHERAL ADMINISTRATION OF AGMATINE IN THE RAT

Agonists specific for the I-1 imidazoline receptor increase sodium exc retion following intrarenal (ir) infusion or intracerebroventricular ( icy) injection in the rat. Although agmatine has been suggested to be a putative endogenous agonist for these receptors, the ability of this compound to alter sodium excretion has not been determined. The effec ts of agmatine, whether administered ir or icy, on blood pressure and solute and water excretion were studied in Sprague-Dawley rats. Agmati ne was administered by icy injection (0, 10, 100, 300 or 1,000 nmol in 5 mu l) or by direct ir infusion (0, 3, 10, 30 or 100 nmol/kg/m in at 3.4 mu l/min) in pentobarbitone-anesthetized rats. Agmatine administe red by icy injection or ir infusion did not alter blood pressure or he art rate. Only an ir infusion of agmatine produced an increase in crea tinine clearance, which occurred at the lowest (3 nmol/kg/min) and hig hest dose (100 nmol/kg/min). Concomitantly, the ir infusion of agmatin e produced a dose-related increase in urine flow rate, but both routes of administration were associated with an increase in sodium excretio n and osmolar clearance. Similar to previous reports with I-1 imidazol ine receptor-selective compounds, agmatine increased urine flow rate s econdary to an increase in osmolar clearance at doses that failed to a lter blood pressure. These results were consistent with agmatine funct ioning as a physiological agonist resulting in alterations in sodium e xcretion.