RT Journal Article
SR Electronic
T1 Increased Expression of the Sodium Transporter BSC-1 in Spontaneously Hypertensive Rats
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 1052
OP 1061
DO 10.1124/jpet.104.071209
VO 311
IS 3
A1 Prajakta A. Sonalker
A1 Stevan P. Tofovic
A1 Edwin K. Jackson
YR 2004
UL http://jpet.aspetjournals.org/content/311/3/1052.abstract
AB The purpose of this study was to compare the expression of BSC-1 (bumetanide-sensitive Na+-K+-2Cl– cotransporter) in kidneys of spontaneously hypertensive rats (SHR) versus Wistar-Kyoto (WKY) rats by immunoblotting and reverse transcription-polymerase chain reaction. To determine the specificity of any observed changes in BSC-1 expression, we also compared expression of the thiazide sensitive Na+-Cl– cotransporter (TSC), the type-3 Na+-H+ exchanger (NHE-3), Na+-K+-ATPase-α1, the inwardly rectifying K+ channel (ROMK-1), the type-1 \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(\mathrm{Na}^{+}\mathrm{-}\mathrm{HCO}_{3}^{-}\) \end{document} cotransporter (NBC-1), aquaporin-1, and aquaporin-2. Analyses were performed on outer cortex, outer medulla, and inner medulla. BSC-1 protein was detected in outer medulla and was markedly (6-fold) higher in SHR. TSC protein was detected in the cortex and was not overexpressed in SHR. Aquaporin-1 protein was detected in all three regions and was not overexpressed in SHR. Aquaporin-2 and ROMK-1 proteins were detected in all three regions, but were moderately elevated (2-fold) only in the SHR inner medulla. Na+-K+-ATPase and NHE-3 proteins were detected in all three regions. Na+-K+-ATPase-α1 was modestly (25%) increased in SHR outer and inner medulla, whereas NHE-3 was moderately (2-fold) increased in the SHR cortex and inner medulla. NBC-1 protein was detected only in the cortex and was higher (2-fold) in SHR. mRNA levels of BSC-1, aquaporin-2, and ROMK-1 were not elevated in SHR, indicating a post-translational mechanism of protein overexpression. High-dose furosemide increased fractional sodium excretion more in SHR than WKY (3-fold). We conclude that increased expression of BSC-1, and to a lesser extent, aquaporin-2, ROMK-1, NHE-3, and NBC-1 may contribute to the pathogenesis of hypertension in the SHR. The American Society for Pharmacology and Experimental Therapeutics