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(Hypertension. 2007;49:1186.)
© 2007 American Heart Association, Inc.

Original Articles

Activity and Regulation of Na⁺-HCO₃^– Cotransporter in Immortalized Spontaneously Hypertensive Rat and Wistar–Kyoto Rat Proximal Tubular Epithelial Cells

Rui Pedrosa; Nuno Gonçalves; Ulrich Hopfer; Pedro A. Jose; Patrício Soares-da-Silva

From the Institute of Pharmacology and Therapeutics Faculty of Medicine (R.P., N.G., P.S.d.S.), Porto, Portugal; the Department of Physiology and Biophysics (U.H.), Case Western Reserve School of Medicine, Cleveland, Ohio; and the Department of Pediatrics (P.A.J.), Georgetown University, Washington, DC.

Correspondence to Patrício Soares-da-Silva, Institute of Pharmacology and Therapeutics, Faculty of Medicine, 4200-319 Porto, Portugal. E-mail psoaresdasilva{at}netcabo.pt

The present study evaluates the presence and functional proprieties of the Na⁺-HCO₃^– cotransporter (NBC) in immortalized renal proximal tubular epithelial cells from spontaneously hypertensive (SHR) and normotensive Wistar–Kyoto (WKY) rats. The expected size and nucleotide sequence of a 1031-bp fragment corresponding to type 1 NBC (NBC1) was identified in both cell lines. The expression of the NBC1 transcript was lower (P<0.05) in SHR than in WKY cells. After intracellular acidification and in the presence of amiloride (1 mmol/L), the addition of sodium (115 mmol/L) in the absence of chloride resulted in rapid intracellular pH recovery that was higher in WKY than in SHR cells. This was an Na⁺- and HCO₃^–-dependent process in both cell lines. 4,4'-Diisothiocyanatodihydrostilbene-2,2'-disulphonic acid inhibited NBC activity in both WKY and SHR cells; the inhibitory effect was, however, more pronounced in WKY than in SHR cells. Forskolin (10 µmol/L) and dibutyryl cAMP (0.5 mmol/L) did not alter NBC activity. Acidosis induced by a 24-hour treatment with NH4⁺ (20 mmol/L) increased NBC activity to a greater extent in SHR than in WKY cells, without changes in intracellular pH and cell viability. Treatment with acetazolamide (300 µmol/L) for 24 hours did not change NBC activity in both cell lines. In contrast to NBC, Na⁺-K⁺ ATPase activity and expression were higher in SHR than in WKY cells. It is concluded that SHR cells are endowed with lower NBC activity than WKY cells, but the former is more resistant to 4,4'-diisothiocyanatodihydrostilbene-2,2'-disulphonic acid and responds better to acidosis.

Key Words: Na⁺-HCO₃^– • cotransporter • hypertension • acidosis • SHR • WKY