Effect of prostaglandin synthesis inhibitors on clonidine-induced diuresis in rats.
Clonidine is a centrally acting antihypertensive drug that also has marked renal effects. The role of renal prostaglandins in clonidine-induced diuresis was examined in anesthetized and conscious rats. Twelve surgically prepared rats were pretreated with either of two inhibitors of prostaglandin synthesis, indomethacin or meclofenamate (2 mg/kg), while thirteen rats served as controls. Clonidine (200 micrograms/kg/hr, i. v.) increased urine flow tenfold in both pretreated and nonpretreated controls whereas blood pressure and glomerular filtration rate were reduced by clonidine. Fractional excretions of sodium, potassium, total solute and water were enhanced similarly in these two groups of anesthetized rats. Experiments were also conducted in ten conscious rats pretreated with vehicle, indomethacin (2.0 and 7.5 mg/kg), or meclofenamate (2 mg/kg) prior to clonidine infusion. Marked diuresis occurred whether these rats were pretreated with vehicle or one of the nonsteroidal antiinflammatory drugs (NSAID). Thus, NSAID did not prevent the renal excretory response to clonidine in either anesthetized or conscious rats, suggesting that enhanced prostaglandin synthesis is not an essential component of the diuretic action of this drug in rats.
D000758:Anesthesia; D000818:Animals; D003000:Clonidine / Q000494:pharmacology*; D004231:Diuresis / Q000187:drug effects*; D008297:Male; D011188:Potassium / Q000378:metabolism; D011453:Prostaglandins / Q000096:biosynthesis*; D051381:Rats; D012964:Sodium / Q000378:metabolism
D011453:Prostaglandins; D012964:Sodium; D003000:Clonidine; D011188:Potassium