Suppression of antidiuretic hormone secretion by clonidine in the anesthetized dog.
Studies were performed to determine the mechanism by which the antihypertensive agent clonidine increases urine flow (V). In 11 anesthetized, hydropenic dogs, i.v. administration of clonidine (30 mug/kg) increased arterial pressure from 128 +/- 4 to 142 +/- 3 mm Hg and slowed heart rate from 138 +/- 7 to 95 +/- 7 beats/min within 30 min of injection; blood pressure then fell to 121 +/- 5 mm Hg 30 to 60 min after injection, and 112 +/- 5 mm Hg in the next 30-min period. V increased from 0.36 +/- 0.09 to 0.93 +/- 0.13 Uosm ml/min and urine osmolality (Uopsm) decreased from 1378 +/- 140 to 488 +/- 82 mOsm/kg of H2O 30 to 60 min following injection (P less than 0.001). These changes were accompanied by a decrease in TcH20. This increased V was not associated with increased glomerular filtration rate (GFR) or solute excretion, and occurred in acutely denervated kidneys and kidneys protected from the initial increase in arterial pressure by constriction of a suprarenal aortic clamp. By contrast, V TcH2O and UOsm were not altered by clonidine administration in seven acutely hypophysectomized dogs receiving a constant infusion of antidiuretic hormone (ADH) (80 muU/kg/min), despite similar hemodynamic changes produced by the drug. The results suggest that clonidine increases V through inhibition of ADH release, possibly via an indirect pathway mediated by the drug's alpha-adrenergic on the circulation.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003000:Clonidine / Q000494:pharmacology*; D003681:Dehydration / Q000503:physiopathology / Q000652:urine; D003864:Depression, Chemical; D004231:Diuresis; D004285:Dogs; D005919:Glomerular Filtration Rate; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D007016:Hypophysectomy; D007668:Kidney / Q000294:innervation; D008297:Male; D009994:Osmolar Concentration; D011188:Potassium / Q000097:blood; D012039:Regional Blood Flow / Q000187:drug effects; D014556:Urine; D014667:Vasopressins / Q000378:metabolism*; D014882:Water-Electrolyte Balance / Q000187:drug effects
D014667:Vasopressins; D003000:Clonidine; D011188:Potassium