Effect of diuretics on sodium and chloride permeability in the rat papillary collecting duct.
While in vivo data suggests that diuretics such as furosemide and hydrochlorothiazide alter inner medulla collecting duct (IMCD) cell electrolyte transport, this has not been confirmed by in vivo studies nor have the mechanisms been evaluated. This study evaluated the direct effect of these diuretics as well as amiloride on sodium and chloride unidirectional permeability in the isolated perfused rat IMCD. In the absence of diuretics, the permeability of sodium was lower than that of chloride (0.63 +/- 0.05 compared with 0.83 +/- 0.08 micrometer/s), although both were relatively impermeable when compared to water. Furosemide (10(-4)) and hydrochlorothiazide (10(-3)) both increased the diffusional permeability of chloride by approximately 30% (0.80 +/- 0.06 to 1.04 +/- 0.09 micrometer/s, p < 0.01, and 0.74 +/- 0.09 to 0.98 +/- 0.10 micrometer/s, p < 0.02, respectively). However, sodium permeability was unaltered. Inhibition of Na+, K+-ATPase by ouabain or cooling (4 degrees C) inhibited basal sodium but not chloride permeability while a maximal antidiuretic AVP concentration did not alter sodium or chloride permeability. However, increasing the lumen and bath sodium chloride concentration from 150 to 300 and 600 mM significantly increased both sodium and particularly chloride conductance. In contrast, amiloride (10(-4)) significantly reduced both sodium and chloride permeability. These studies support a direct effect of furosemide and hydrochlorothiazide on the IMCD and suggest that their in vivo effect is primarily mediated by facilitating the passive movement of chloride into the lumen via a favourable electrochemical gradient. These results also demonstrate that amiloride inhibits both sodium and chloride unidirectional permeability by mechanisms separate to that of the sulphonamide-related diuretics.
Ray
C
C
Discipline of Medicine, Faculty of Medicine and Health Sciences, University of Newcastle, N.S.W., Australia.
Carney
S
S
Gillies
A
A
D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D002712:Chlorides / Q000493:pharmacokinetics*; D004232:Diuretics / Q000494:pharmacology*; D005260:Female; D005665:Furosemide / Q000494:pharmacology; D006852:Hydrochlorothiazide / Q000494:pharmacology; D066298:In Vitro Techniques; D007444:Inulin / Q000378:metabolism; D007685:Kidney Tubules, Collecting / Q000378:metabolism*; D008297:Male; D010539:Permeability; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000493:pharmacokinetics*; D049993:Sodium Chloride Symporter Inhibitors / Q000494:pharmacology
D002712:Chlorides; D004232:Diuretics; D049993:Sodium Chloride Symporter Inhibitors; D006852:Hydrochlorothiazide; D000584:Amiloride; D005665:Furosemide; D007444:Inulin; D012964:Sodium