Inhibition of Ca absorptive flux by chlorthalidone in the rat duodenum and colon

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 · kg^-1 · 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 < 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 (J(m→s)) (96.7 vs. 111.5 nmol · cm^-2 · h^-1, P < 0.05). Since serosal-to-mucosal flux (J(s→m)) was unchanged, net Ca flux (J(net)) was reduced (74.0 vs. 89.6 nmol · cm^-2 · h^-1, P < 0.05). Similarly, chlorthalidone selectively inhibited J(m→s) in the descending colon (27.0 vs. 36.2 nmol · cm^-2 · h^-1, P < 0.01), reducing J(net) (14.3 vs. 23.2 nmol · cm^-2 · h^-1, P < 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.