Studies with the optically active isomers of the new diuretic drug ozolinone. II. Inhibition by d-ozolinone of furosemide-induced diuresis.
The effect of the non-diuretic dextrorotatory isomer of ozolinone on furosemide-induced diuresis was studied by means of clearance and micropuncture techniques in rats. After intravenous injection, d-ozolinone antagonized the furosemide-induced increase in renal fluid and electrolyte excretion in a dose-related manner. Microperfusion experiments of Henle's loop in vivo revealed that d-ozolinone did not interfere with the action of furosemide at this tubular site. However, d-ozolinone markedly decreased the furosemide to inulin clearance ratio, presumably as a consequence of inhibition of furosemide secretion into the proximal tubules. It is assumed that, in consequence of a high affinity for the proximal organic acid transport system, d-ozolinone depresses proximal tubular furosemide secretion and prevents transfer of this diuretic to the tubular fluid. Thus, under the influence of d-ozolinone, furosemide cannot reach the loop of Henle in sufficient amounts and its diuretic effect is blocked.
D000818:Animals; D004231:Diuresis / Q000187:drug effects*; D004232:Diuretics / Q000494:pharmacology*; D005665:Furosemide / Q000494:pharmacology; D005919:Glomerular Filtration Rate; D007668:Kidney / Q000098:blood supply / Q000502:physiology*; D007687:Kidney Tubules, Proximal / Q000502:physiology; D008138:Loop of Henle / Q000502:physiology; D008297:Male; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D012039:Regional Blood Flow; D013844:Thiazoles / Q000494:pharmacology*
D004232:Diuretics; D010880:Piperidines; D013844:Thiazoles; C018121:ozolinone; D005665:Furosemide