INHIBITION OF THE NATRIURETIC ACTION OF THE IMIDAZOLINE RECEPTOR AGONIST MOXONIDINE BY INDOMETHACIN IN THE RAT

Indometacin pretreatment potentiates the natriuretic action of the mix ed alpha(2)-adrenoceptor/imidazoline receptor agonist clonidine. In th e present study we determined the effects of indometacin pretreatment on natriuretic actions of the selective Ii imidazoline receptor agonis t. 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 intra renal infusion of moxonidine (1 nmol/kg/min) without altering blood pr essure or creatinine clearance. Administration of prostaglandin E(2), at an infusion rate (1 mu g/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 mo xonidine. The ability of indometacin pretreatment to potentiate natriu retic actions of an alpha(2)-adrenoceptor agonist and to attenuate tho se 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.