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Am J Physiol Renal Physiol 261: F452-F458, 1991;
0363-6127/91 $5.00
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AJP - Renal Physiology, Vol 261, Issue 3 452-F458, Copyright © 1991 by American Physiological Society

ARTICLES

Effect of thiazides on colonic NaCl absorption: role of carbonic anhydrase

D. S. Goldfarb, A. J. Chan, D. Hernandez and A. N. Charney
Nephrology Section, Department of Veteran Affairs Medical Center, New York, New York 10010.

The mechanisms by which the benzothiadiazide class of diuretics inhibit electroneutral NaCl absorption are not fully understood. We studied the mechanisms of thiazide action in perfused loops of distal colon in anesthetized male Sprague-Dawley rats. Hydroflumethiazide (1 mM) reversibly inhibited greater than 40% of Na, Cl, and water absorption. Prior exposure of the colon to the carbonic anhydrase inhibitor methazolamide (0.1 mM) prevented the effects of hydroflumethiazide and metolazone, a thiazide-like drug, on colonic absorption. In Ussing flux chambers, addition of hydroflumethiazide to both the mucosal and serosal bathing solutions (but not to the mucosal solution alone) caused marked decreases in Na and Cl absorption. Such inhibition only occurred at concentrations of hydroflumethiazide (0.1 and 1.0 mM) that inhibited greater than 90% of carbonic anhydrase activity in homogenized colonic mucosa. We conclude that an important mechanism by which thiazides inhibit NaCl absorption in the rat distal colon is by inhibition of mucosal carbonic anhydrase. In tissues containing this enzyme, this mechanism of thiazide effect on ion flux must be considered.


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P. Pickkers, R. S. Garcha, M. Schachter, P. Smits, and A. D. Hughes
Inhibition of Carbonic Anhydrase Accounts for the Direct Vascular Effects of Hydrochlorothiazide
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[Abstract] [Full Text] [PDF]


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