Thiazide-sensitive NaCl absorption in rat cortical collecting duct.
The mechanism of transepithelial NaCl transport was investigated in isolated perfused cortical collecting ducts from the kidneys of deoxycorticosterone-treated rats. In the presence of vasopressin, hydrochlorothiazide (0.1 mM) markedly reduced the net rate of Na absorption, Cl absorption, and active fluid absorption but did not significantly change the transepithelial voltage. Similarly, in the absence of vasopressin, hydrochlorothiazide decreased the rate of sodium absorption by 50% without affecting transepithelial voltage. Amiloride (30 microM) completely eliminated the lumen-negative voltage but decreased net sodium absorption only by approximately 50%. In the presence of amiloride, chloride absorption occurred against an electrochemical gradient for chloride, indicating that there was active chloride absorption. Bumetanide (0.1 mM) did not affect chloride absorption or spontaneous fluid absorption in the presence of vasopressin. The combination of amiloride and hydrochlorothiazide inhibited net sodium absorption by a greater extent than did either agent alone. These results demonstrate the presence of the following two parallel sodium transport pathways in cortical collecting ducts from mineralocorticoid-replete rats: 1) an electrogenic pathway blocked by amiloride, which presumably involves an apical sodium channel, and 2) a thiazide-inhibitable electroneutral pathway, which presumably utilizes apical Na-Cl cotransport and mediates secondary active transport of chloride.
Terada
Y
Y
Laboratory of Kidney and Electrolyte Metabolism, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892.
Knepper
M A
MA
D000042:Absorption; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport; D002034:Bumetanide / Q000494:pharmacology; D002712:Chlorides / Q000493:pharmacokinetics; D006852:Hydrochlorothiazide / Q000494:pharmacology*; D007672:Kidney Cortex; D007684:Kidney Tubules / Q000378:metabolism*; D007685:Kidney Tubules, Collecting / Q000378:metabolism*; D008297:Male; D010042:Ouabain / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000493:pharmacokinetics; D012965:Sodium Chloride / Q000493:pharmacokinetics*
D002712:Chlorides; D006852:Hydrochlorothiazide; D002034:Bumetanide; D012965:Sodium Chloride; D010042:Ouabain; D000584:Amiloride; D012964:Sodium