AJP - Renal Physiology, Vol 250, Issue 3 396-F399, Copyright © 1986 by American Physiological Society
Inhibition of Ca absorptive flux by chlorthalidone in the rat duodenum and colon
U. Gafter, K. Lau, J. Garno and S. Kathpalia
To evaluate the mode and intestinal sites of action of chlorthalidone on Ca
transport, balance and flux studies by the Ussing technique were performed
in rats fed a low Ca diet throughout the experiment to stimulate Ca
absorption. Half of the rats received chlorthalidone (5 mg X kg-1 X day-1)
orally for 18 wk, a duration of administration previously shown to yield
consistent changes. Net Ca absorption was decreased by chlorthalidone (0.91
+/- 0.07 vs. 1.08 +/- 0.3 mg/day, P less than 0.05), which is similar to
prior observations in rats fed a normal Ca diet. Ca balance was unchanged
by chlorthalidone (0.34 +/- 0.08 vs. 0.36 +/- 0.05 mg/day) because of
concomitant hypocalciuria of similar magnitudes. In the duodenum,
chlorthalidone decreased mucosal-to-serosal flux (Jm----s) (96.7 vs. 111.5
nmol X cm-2 X h-1, P less than 0.05). Since serosal-to-mucosal flux
(Js----m) was unchanged, net Ca flux (Jnet) was reduced (74.0 vs. 89.6 nmol
X cm-2 X h-1, P less than 0.05). Similarly, chlorthalidone selectively
inhibited Jm----s in the descending colon (27.0 vs. 36.2 nmol X cm-2 X h-1,
P less than 0.01), reducing Jnet (14.3 vs. 23.2 nmol X cm-2 X h-1, P less
than 0.005). Short-circuit current and tissue conductance were unaffected.
These data suggest that chronic chlorthalidone treatment reduces Ca
absorption by inhibiting active calcium transport in the small and large
intestine.
