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.
|Journal||American Journal of Physiology - Renal Fluid and Electrolyte Physiology|
|Issue number||3 (19/3)|
|State||Published - 1986|