Effects of cicletanine on kidney function. 2. Role of renal prostaglandins and kinins, and of muscarinic receptors.

We report the effect of the prostaglandin synthesis inhibitors indomethacin and meclofenamate, of the ACE-inhibitor captopril and of the muscarinic receptor antagonist methyl-scopolamine on the renal action of cicletanine (20-30 mg/kg i.v.) in anesthetized rats. Methylscopolamine, at doses ranging from 60 to 600 micrograms/kg i.v., did not at all affect cicletanine's action on the kidney's excretory function. Captopril (20 mg/kg i.v.) induced by its own a small rise of urine flow, and of urinary sodium and chloride excretion. The drug enhanced the effect of cicletanine on urine flow and sodium excretion by an additive effect. In the presence of captopril, and also of indomethacin (5 mg/kg i.v.) and meclofenamate (5 mg/kg i.v.), but not with control conditions, cicletanine significantly enhanced glomerular filtration rate and p-animohippurate clearance. Despite the fact that renal hemodynamics improved, the prostaglandin inhibitors nearly completely abolished cicletanine's effect on urinary fluid and electrolyte excretion. The results suggest that muscarinic receptors are not involved in the diuretic response to cicletanine. Cicletanine's diuretic and saluretic action may be related to a stimulation of renal prostaglandin synthesis. An enhanced prostaglandin production, and an activated reninangiotensin system, may also mask a direct vasodilating effect of cicletanine on the renal vasculature in the rat.