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Am J Physiol Renal Physiol. 2007 Jun;292(6):F1701-9. Epub 2007 Feb 20.

Chronic furosemide or hydrochlorothiazide administration increases H+-ATPase B1 subunit abundance in rat kidney.

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1
Department of Internal Medicine, Seoul National University College of Medicine, Clinical Research Institute of Seoul National University Hospital, Chongno-gu, Seoul 110-744, South Korea.

Abstract

Furosemide administration stimulates distal acidification. This has been attributed to the increased lumen-negative voltage in the distal nephron, but the aspect of regulatory mechanisms of H(+)-ATPase has not been clear. The purpose of this study is to investigate whether chronic administration of diuretics alters the expression of H(+)-ATPase and whether electrogenic Na(+) reabsorption is involved in this process. A 7-day infusion of furosemide or hydrochlorothiazide (HCTZ) lowered urine pH significantly. However, this effect of furosemide-induced distal acidification was not changed with amiloride-blocking electrogenic Na(+) reabsorption. On immunoblotting, a polyclonal antibody against the H(+)-ATPase B1 subunit recognized a specific approximately 56-kDa band in membrane fractions from the kidney. The protein abundance of H(+)-ATPase was significantly increased by furosemide and HCTZ infusion in both the cortex and outer medulla. Furosemide plus amiloride administration also increased the H(+)-ATPase protein abundance significantly. However, no definite subcellular redistribution of H(+)-ATPase was observed by furosemide +/- amiloride infusion with immunohistochemistry. Chronic furosemide +/- amiloride administration induced a translocation of pendrin to the apical membrane, while total protein abundance was not increased. The mRNA expression of H(+)-ATPase was not altered by furosemide +/- amiloride infusion. We conclude that chronic administration of diuretics enhances distal acidification by increasing the abundance of H(+)-ATPase irrespective of electrogenic Na(+) reabsorption. This upregulation of H(+)-ATPase in the intercalated cells may be the result of tubular hypertrophy by diuretics.

PMID:
17311909
DOI:
10.1152/ajprenal.00270.2006
[Indexed for MEDLINE]
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