Carbonic Anhydrase II Deletion Confers Salt Appetite and Elicits Adaptive Regulation of Salt and Water Transporters in the Kidney

Abstract

BackgroundSalt appetite, which is salt craving or salt intake in excess of physiological needs, is regulated by a number of physiological mechanisms including neuronal and hormonal pathways. Excess salt intake is a major health problem and a risk factor for many diseases, including hypertension. Few genetic factors are implicated in the pathogenesis of salt appetite.Methods and ResultsHere we demonstrate that mice with the genetic inactivation of carbonic anhydrase 2 (CAII) display significant salt appetite as judged by their preference for salted water (280 mM NaCl added to the drinking water) over regular tap water, when both options are provided (average daily salted water intake of 2.80 ml in WT and 5.2 ml in CAII KO mice, p<0.01, n=5 while daily tap water intake was 4.2 ml in WT and 2.8 ml in CAII KO mice, p<0.03, n=5). The excess salt intake was observed in the absence of any vascular volume depletion or kidney dysfunction, as judged by comparable kidney renin expression and blood creatinine and BUN concentration levels in WT and CAII KO mice, and was more profound in male mice. When only provided the salted water (280 mM salt added to the drinking water), CAII null animals showed a robust increase in daily water intake vs. WT mice (20.54 ml in KO mice vs. 11.83 ml in WT, p<0.001, n=5) as well as an increase in sodium excretion (0.192 mmol/g in CAII KO vs. 0.0716 mmol/g in WT, p<.01, n=5). The expression levels of kidney sodium and water absorbing channels ENaC and AQP‐2, determined by western blotting and northern hybridization, showed robust increases (ranging from 100 to 200%) in response to enhanced salt intake in CAII KO mice vs. wild type littermates. The AVP expression levels in pituitary gland significantly increased in CAII KO mice vs. WT littermates when receiving salted water for 10 days (p<0.05), despite their comparable expression levels at baseline conditions. We propose that CAII plays an important role in regulating salt intake and its inactivation can cause salt appetite, specifically in male animals.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.