Altered drinking responses in dogs with chronic metabolic alkalosis.

Abstract

Chronic chloride depletion alkalosis in dogs causes a lowered osmotic threshold and increased sensitivity for vasopressin (AVP) release. Since AVP release and drinking behavior normally are closely associated over a narrow range of changes in plasma osmolality (Posm), we investigated whether alkalotic dogs would also show an altered responsiveness to the dipsogenic effects of angiotensin II (ANG II) and osmotic stimuli. Dogs made chronically alkalotic by a combination of chloride-free diet and furosemide injections developed polydipsia in the absence of any increase in solute intake and in the presence of a significant reduction in Posm. The animals were chronically hypochloremic, hyponatremic and hypokalemic, and appeared to be extracellular fluid (ECF) contracted. Plasma renin activity (PRA) was 10-fold higher in alkalotic dogs than controls. When Posm was increased by a slow 2 hr infusion of hypertonic sodium sulfate, alkalotic dogs were found to have a significantly lower osmotic threshold for inducing drinking (289.8 +/- 1.1 mOsm/kg/H2O vs. 305.1 +/- 1.3 mOsm/kg/H2O in controls), but the slope or sensitivity of the water intake/Posm relationship was not significantly different. Finally, compared to normal animals, alkalotic dogs were unresponsive to the dipsogenic effects of IV ANG II. These data indicate that the central mechanisms which mediate drinking in response to cellular and extracellular thirst stimuli are altered in chronic metabolic alkalosis.