title: Increased expression of the sodium transporter BSC-1 in spontaneously hypertensive rats.
abstract: 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-alpha1, the inwardly rectifying K+ channel (ROMK-1), the type-1 Na+-HCO3- 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-alpha1 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.
authors.affiliation: Center for Clinical Pharmacology, University of Pittsburgh Medical Center, 623 Scaife Hall, 3550 Terrace Street, Pittsburgh, Pennsylvania 15261, USA.
authors.forename: Prajakta A
authors.initials: PA
authors.lastname: Sonalker
authors.forename: Stevan P
authors.initials: SP
authors.lastname: Tofovic
authors.forename: Edwin K
authors.initials: EK
authors.lastname: Jackson
mesh_terms: D000818:Animals; D020346:Aquaporins / Q000096:biosynthesis / Q000235:genetics; D004232:Diuretics / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D005665:Furosemide / Q000494:pharmacology; D006973:Hypertension / Q000378:metabolism*; D015151:Immunoblotting; D007679:Kidney Medulla / Q000378:metabolism; D008297:Male; D024661:Potassium Channels, Inwardly Rectifying / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics / Q000302:isolation & purification; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D020133:Reverse Transcriptase Polymerase Chain Reaction; D027982:Sodium-Bicarbonate Symporters / Q000096:biosynthesis / Q000235:genetics; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers / Q000096:biosynthesis / Q000235:genetics; D028021:Sodium-Potassium-Chloride Symporters / Q000096:biosynthesis* / Q000235:genetics; D000254:Sodium-Potassium-Exchanging ATPase / Q000096:biosynthesis / Q000235:genetics; D064466:Solute Carrier Family 12, Member 1
chemical_list: D020346:Aquaporins; D004232:Diuretics; D024661:Potassium Channels, Inwardly Rectifying; D012333:RNA, Messenger; C578716:Slc12a1 protein, rat; C422004:Slc4a4 protein, rat; C000613387:Slc9a3 protein, rat; D027982:Sodium-Bicarbonate Symporters; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers; D028021:Sodium-Potassium-Chloride Symporters; D064466:Solute Carrier Family 12, Member 1; D005665:Furosemide; C499075:Atp1a1 protein, rat; D000254:Sodium-Potassium-Exchanging ATPase