Sodium excretion following central administration of an I1 imidazoline receptor agonist, moxonidine.
1. Previously we have shown that an intrarenal infusion of moxonidine, an I1-imidazoline receptor agonist, resulted in a natriuresis which was inhibited by intravenous idazoxan, a selective imidazoline receptor antagonist. Therefore we examined the effects of renal function of intracerebroventricular (i.c.v.) administration of moxonidine with or without i.c.v. idazoxan. 2. Seven days after unilateral nephrectomy, Sprague-Dawley rats had i.c.v. cannulae implanted. Three days later the rats were anaesthetized (pentobarbitone), followed by cannulation of the jugular vein (fluid and drug administration), carotid artery (blood pressure) and the ureter (urine collection). 3. After a 45 min stabilization period, the effect of moxonidine was investigated by the i.c.v. administration of either isotonic saline or moxonidine (0.1, 0.3 or 1 nmol in isotonic saline) administered in 5 microliters over 1 min. All doses of moxonidine resulted in an increase in urine flow with a concomitant increase in sodium excretion without affecting blood pressure. The highest dose of moxonidine (1 nmol) also increased free water clearance. 4. In a second series of experiments, the effects of idazoxan on the natriuretic 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 excretion, completely attenuated the renal response to moxonidine. These results are consistent with central I1-imidazoline receptors mediating a moxonidine-induced increase in sodium and water excretion at doses that do not alter blood pressure.
Department of Pharmacology & Therapeutics, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
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Penner
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Smyth
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000187:drug effects*; D004146:Dioxanes / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D019329:Idazoxan; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D054755:Imidazoline Receptors; D007276:Injections, Intraventricular; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011955:Receptors, Drug / Q000819:agonists*; D012964:Sodium / Q000652:urine*
D004146:Dioxanes; D007093:Imidazoles; D054755:Imidazoline Receptors; D011955:Receptors, Drug; D012964:Sodium; C043482:moxonidine; D019329:Idazoxan