CLONIDINE-INDUCED DIURESIS IN THE RAT - EVIDENCE FOR A RENAL SITE OF ACTION

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  • 1 January 1980
    • journal article
    • research article
    • Vol. 214  (3) , 608-613
Abstract
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 to another mechanism of action. Heterozygous rats given clonidine s.c. in doses of 50-300 .mu.U/kg body wt exhibited a prompt dose-related diuresis. The diuresis was transient and could not be maintained beyond 4 h 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[milliosmole]/kg by 60 min after injection. Baseline plasma ADH was 5.1 .+-. 0.9 .mu.U/ml, remained unchanged at 15 min after clonidine injection but increased to 21.6 .+-. 7.2 .mu.U/ml by 60 min and was accompanied by an increase in urinary ADH excretion from 19.6 .+-. 3.7 to 48.6 .+-. 5.3 .mu.U/h. In parallel with the drug-induced diuresis, there was an increase in urinary excretion of creatinine, Na and total solute. The .alpha.-blocking agent phenoxybenzamine did not prevent the diuresis after clonidine injection. Clonidine antagonized the antidiuretic action of ADH administered to rats homozygous for diabetes insipidus. Clonidine-induced diuresis is probably not due to .alpha. adrenergic inhibition of ADH release but to direct renal effects.