Organ specific underexpression renal of Na+-dependent B0AT1 in the SHR correlates positively with overexpression of NHE3 and salt intake.
The present study examines the renal and intestinal expression of Na(+)-dependent amino acid transporter B(0)AT1 during the development of hypertension in the spontaneous hypertensive rats (SHR) and its normotensive control (Wistar-Kyoto rat; WKY), and evaluates whether the expression of renal B(0)AT1 correlates with changes in the expression of Na(+) transporters, type 3 Na(+)/H(+) exchanger (NHE3) and Na(+)-K(+)-ATPase, known to occur in the SHR. The effect of high salt (HS) intake on the expression of renal and intestinal B(0)AT1 transcript abundance was also evaluated. For this purpose, the cloning of rat homolog of B(0)AT1 was performed. Rat B(0)AT1 shows high sequence homology to the mouse ortholog. Renal B(0)AT1 transcript abundance was lower in SHR than WKY at both 4 and 12 weeks of age. No significant differences between strains were observed in terms of intestinal expression of B(0)AT1. The decreased B(0)AT1 expression in SHR kidney was accompanied with an increase in NHE3 expression, suggesting an impaired Na(+) uptake. HS intake decreased renal B(0)AT1 mRNA in SHR and WKY at 4 weeks of age. In 12-week-old SHR, HS intake increased renal B(0)AT1 transcript abundance. Intestinal B(0)AT1 transcript was significantly increased by HS intake, though the effect was considerably more pronounced in the SHR. It is concluded, that underexpression of B(0)AT1 in the SHR kidney is organ specific, precedes the onset of hypertension and correlates negatively with the renal tubular transport of Na(+). The regulation of B(0)AT1 gene transcription appears to be under the influence of Na(+) delivery, being organ specific.
Pinho
Maria João
MJ
Faculty of Medicine, Institute of Pharmacology and Therapeutics, 4200 Porto, Portugal.
Serrão
Maria Paula
MP
José
Pedro A
PA
Soares-da-Silva
Patrício
P
D000595:Amino Acid Sequence; D026921:Amino Acid Transport Systems, Neutral / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D000818:Animals; D015151:Immunoblotting; D007684:Kidney Tubules / Q000378:metabolism*; D027283:Large Neutral Amino Acid-Transporter 1 / Q000378:metabolism; D008969:Molecular Sequence Data; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D012964:Sodium / Q000378:metabolism*; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage*; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics / Q000378:metabolism
D026921:Amino Acid Transport Systems, Neutral; D027283:Large Neutral Amino Acid-Transporter 1; C520324:SLC6A19 protein, rat; C000613386:Slc9a3 protein, mouse; C000613387:Slc9a3 protein, rat; D017673:Sodium Chloride, Dietary; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase