SODIUM-EXCRETION FOLLOWING CENTRAL ADMINISTRATION OF AN I-1 IMIDAZOLINE RECEPTOR AGONIST, MOXONIDINE

1 Previously we have shown that an intrarenal infusion of moxonidine, an I-1-imidazoline receptor agonist, resulted in a natriuresis which w as inhibited by intravenous idazoxan, a selective imidazoline receptor antagonist. Therefore we examined the effects on renal function of in tracerebroventricular (i.c.v.) administration of moxonidine with or wi thout i.c.v. idazoxan. 2 Seven days after unilateral nephrectomy, Spra gue-Dawley rats had i.c.v. cannulae implanted. Three days later the ra ts were anaesthetized (pentobarbitone), followed by cannulation of the jugular vein (fluid and drug administration), carotid artery (blood p ressure) and the ureter (urine collection). 3 After a 45 min stabiliza tion period, the effect of moxonidine was investigated by the i.c.v. a dministration of either isotonic saline or moxonidine (0.1, 0.3 or 1 n mol in isotonic saline) administered in 5 mu l over 1 min. All doses o f moxonidine resulted in an increase in urine flow with a concomitant increase in sodium excretion without affecting blood pressure. The hig hest dose of moxonidine (1 nmol) also increased free water clearance. 4 In a second series of experiments, the effects of idazoxan on the na triuretic response to i.c.v. moxonidine were determined. Moxonidine (0 .3 nmol) again increased sodium and water excretion as compared to the i.c.v. saline control animals. Pretreatment with i.c.v. idazoxan (0.3 nmol), at a dose which alone failed to alter sodium and water excreti on, completely attenuated the renal response to moxonidine. These resu lts are Consistent with central I-1-imidazoline receptors mediating a moxonidine-induced increase in sodium and water excretion at doses tha t do not alter blood pressure.