Inhibition of the natriuretic action of the imidazoline receptor agonist moxonidine by indometacin in the rat.
Indometacin pretreatment potentiates the natriuretic action of the mixed alpha 2-adrenoceptor/imidazoline receptor agonist clonidine. In the present study we determined the effects of indometacin pretreatment on natriuretic actions of the selective I1 imidazoline receptor agonist. In anaesthetized rats, an intrarenal infusion of moxonidine (0, 0.3, 1, and 3 nmol/kg/min) increased urine flow rate and sodium excretion without altering blood pressure or creatinine clearance. Indometacin pretreatment abolished the subsequent natriuretic response to an intrarenal infusion of moxonidine (1 nmol/kg/min) without altering blood pressure or creatinine clearance. Administration of prostaglandin E2, at an infusion rate (1 microgram/kg/min) which alone failed to alter urine flow rate, sodium excretion, blood pressure, or creatinine clearance, partially, but not completely, restored the natriuretic response to moxonidine. The ability of indometacin pretreatment to potentiate natriuretic actions of an alpha 2-adrenoceptor agonist and to attenuate those of an imidazoline agonist indicates that these two receptors in the kidney are unique and may serve distinct functions in the regulation of sodium and water excretion.
Darkwa
F K
FK
Department of Pharmacology and Therapeutics, University of Manitoba, Winnipeg, Canada.
Smyth
D D
DD
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D003000:Clonidine / Q000494:pharmacology; D003404:Creatinine / Q000652:urine; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism; D004347:Drug Interactions; D007093:Imidazoles / Q000494:pharmacology; D054755:Imidazoline Receptors; D007213:Indomethacin / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects; D008297:Male; D009318:Natriuresis / Q000187:drug effects*; D011188:Potassium / Q000652:urine; D051381:Rats; D017207:Rats, Sprague-Dawley; D011955:Receptors, Drug / Q000819:agonists*
D000316:Adrenergic alpha-Agonists; D000959:Antihypertensive Agents; D016861:Cyclooxygenase Inhibitors; D007093:Imidazoles; D054755:Imidazoline Receptors; D011955:Receptors, Drug; D003404:Creatinine; C043482:moxonidine; D015232:Dinoprostone; D003000:Clonidine; D011188:Potassium; D007213:Indomethacin