The renal effects of clonidine in unanesthetized rats.
Clonidine s.c. (0.01-0.3 mg/kg), in unanesthetized rats, caused an initial rise (+20 mm Hg), followed by a continuous fall of BP and a dose-dependent natriuresis and diuresis for up to 2 h. Glomerular filtration rate (GFR) (CIn) increased during the first 20 min, while effective renal plasma flow (ERPF) (CPAH) remained normal. Subsequently, between 20 and 60 min after injection, ERPF (CPAH) decreased considerably while GFR had reverted to its normal value. In saline-infused rats clonidine diuresis was accompanied by an "inappropriate" positive free water clearance. Pentobarbital anesthesia suppressed the initial BP peak and the diuresis. Phenoxybenzamine (1 mg/kg i.v.) was antinatriuretic in saline diuresis; the effect of phenoxybenzamine + clonidine on diuresis and salt excretion represented the sum of the effects of both drugs, but phenoxybenzamine enhanced the clonidine-induced increase of GFR. Neither haloperidol (1 mg/kg i.v.) nor bulbocapnine (3 mg/kg i.v.) interfered with the renal effects of clonidine. Clonidine s.c. caused hyperglycemia and glucosuria which did not account for the natriuresis. Clonidine thus appears to increase the GFR and "filtration fraction" (FF) by a phenoxybenzamine-insensitive rise of glomerular ultrafiltration, to depress ERPF by alpha-adrenergic afferent vasoconstriction, to induce natriuresis by a tubular action not blocked by phenoxybenzamine and to exert an antivasopressin effect, either by depressing pituitary vasopressin secretion or the renal response to vasopressin.
D000818:Animals; D001060:Aporphines / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D003000:Clonidine / Q000494:pharmacology*; D004231:Diuresis / Q000187:drug effects; D004298:Dopamine / Q000494:pharmacology; D005260:Female; D006220:Haloperidol / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects*; D008297:Male; D010643:Phenoxybenzamine / Q000494:pharmacology; D011188:Potassium / Q000652:urine; D051381:Rats; D013997:Time Factors
D001060:Aporphines; D010643:Phenoxybenzamine; D006220:Haloperidol; D003000:Clonidine; D011188:Potassium; D004298:Dopamine