Clonidine-induced diuresis in the rat: evidence for a renal site of action.
Clonidine, an alpha adrenergic agonist which causes a diuresis in experimental animals, was studied in unanesthetized, conscious Brattleboro rats heterozygous or homozygous for hereditary hypothalamic diabetes insipidus to determine if the diuresis was due to alpha adrenergic inhibition of antidiuretic hormone (ADH) release or to another mechanism of action. Heterozygous rats given clonidine s.c. in doses of 50 to 300 mu/kg b.w. exhibited a prompt dose-related diuresis. The diuresis was transient and could not be maintained beyond 4 hr even when clonidine was administered continuously by s.c. osmotic minipump. In response to clonidine-induced diuresis, plasma osmolality increased acutely from 300 +/- 1 to 310 +/- 1 mOsM/kg by 60 min after injection. Base-line plasma ADH was 5.1 +/- 0.9 mu/ml, remained unchanged at 15 min after clonidine injection but increased to 21.6 +/- 7.2 muU/ml by 60 min and was accompanied by an increase in urinary ADH excretion from 19.6 +/- 3.7 to 48.6 +/- 5.3 muU/hr. In parallel with the drug-induced diuresis, there was an increase in urinary excretion of creatinine, sodium and total solute. The alpha blocking agent phenoxybenzamine did not prevent the diuresis after clonidine injection. Clonidine antagonized the antidiuresis after clonidine injection. Clonidine antagonized the antidiuretic action of ADH administered to rats homozygous for diabetes insipidus. Thus, clonidine-induced diuresis does not appear to be due to alpha adrenergic inhibition of ADH release but rather to direct renal effects.
D000818:Animals; D003000:Clonidine / Q000494:pharmacology*; D003404:Creatinine / Q000652:urine; D003919:Diabetes Insipidus / Q000503:physiopathology; D004231:Diuresis / Q000187:drug effects*; D004573:Electrolytes / Q000652:urine; D007668:Kidney / Q000187:drug effects*; D008297:Male; D009994:Osmolar Concentration; D010643:Phenoxybenzamine / Q000494:pharmacology; D051381:Rats; D014667:Vasopressins / Q000378:metabolism
D004573:Electrolytes; D010643:Phenoxybenzamine; D014667:Vasopressins; D003404:Creatinine; D003000:Clonidine