Thiazide induces water absorption in the inner medullary collecting duct of normal and Brattleboro rats

The reduction of urinary volume after the use of thiazide in the treatment of diabetes insipidus (DI) is known as the "paradoxical effect." Since enha nced proximal solute and water reabsorption only partially account for the reduction in urinary volume, an additional diuretic effect on nephron termi nal segments was postulated. Thus the aim of our work was to investigate th e effect of hydrochlorothiazide (HCTZ) on water transport in the inner medu llary collecting duct (IMCD) of normal and Brattleboro rats. Osmotic water permeability (P-f) and diffusional water permeability (P-dw) were studied a t 37 degrees C and pH 7.4 by the in vitro microperfusion technique. In the absence of antidiuretic hormone (ADH), HCTZ (10(-6) M) added to the perfuse d fluid enhanced P-f from 6.36 +/- 0.56 to 19.08 +/-: 1.70 mu m/s (P < 0.01 ) and P-dw from 38.01 +/- 4.52 to 52.26 +/- 4.38 x 10(-5) cm/s (P < 0.01) i n normal rats and also stimulated P-f in Brattleboro rats from 3.53 +/- 1.4 1 to 11.16 +/- 1.13 mu m/s (P < 0.01). Prostaglandin E-2 (PGE(2)) (10(-5) M ) added to the bath fluid inhibited HCTZ-stimulated P-f (in mu m/s) as foll ows: control, 16.93 +/- 2.64; HCTZ, 29.65 +/- 5.67; HCTZ+PGE(2) 10.46 +/- 1 .84 (P < 0.01); recovery, 16.77 +/- 4.07. These data indicate that thiazide s enhance water absorption in IMCD from normal rats (in the absence of ADH) and from Brattleboro rats and that the HCTZ-stimulated P-f was partially b locked by PGE(2). Thus we may conclude that the effect of thiazide in the t reatment of DI occurs not only in the Na+-Cl- cotransport in the distal tub ule but also in the IMCD.