IMIDAZOLINE RECEPTOR-MEDIATED NATRIURESIS - CENTRAL AND OR PERIPHERALEFFECT/

The ability of imidazoline agonists, such as moxonidine and rilmenidin e, to lower blood pressure has been attributed to a central effect res ulting in a decrease in peripheral sympathetic nerve activity. A simil ar decrease in sympathetic nerve activity to the kidney has been propo sed to explain the increase in sodium excretion. The observed increase in sodium excretion following an intrarenal infusion of moxonidine or rilmenidine suggested the existence of a direct renal action. We ther efore tested the hypothesis that direct renal infusions were acting at a central rather than a peripheral site. Thus, interventions which wo uld decrease the natriuretic effects of central administered moxonidin e would also block the effects of intrarenal administered moxonidine. Studies were performed in anesthetized Sprague-Dawley rats (280-320 g) which had undergone unilateral nephrectomy 7 to 10 days prior to the experiment. The interventions utilized resulted in minimal effects on blood pressure and creatinine clearance. Intracerebroventricular (icv) or intrarenal (ir) administration of moxonidine produced a significan t increase in urine flow rate and sodium excretion. Intravenous (iv) p razosin was used to block the ability of the sympathetic nerves to alt er sodium excretion secondary to alpha(1)-adrenoceptor stimulation. Pr azosin prevented the natriuresis following icy moxonidine but only par tially antagonized the effects of ir moxonidine. To determine if centr al imidazoline receptors mediated the effects of moxonidine, animals w ere pretreated with icy idazoxan. Following icy idazoxan, the effects of icy moxonidine were blocked, whereas the response to intrarenal mox onidine was only partially blocked. Peripheral (iv) administration of idazoxan blocked the actions of intrarenal moxonidine but left the res ponse to icy moxonidine intact. Finally, chemical sympathectomy with r eserpine did not alter the response to intrarenal moxonidine suggestin g that this effect was independent of the sympathetic nervous system. In conclusion, these studies indicate the ability of central and perip heral moxonidine to increase urine flow rate through sodium excretion at two unique sites of action, one central and the other one periphera l, most conceivably within the kidney. (C) 1998 Elsevier Science B.V. All rights reserved.