Altered expression of Na+ transporters at the mRNA level in rat normal and hypertrophic myocardium.
Intracellular Na(+) ([Na(+)](i)) regulation plays a crucial role in the structural, mechanical, and electrical properties of myocardium. It is assumed that the [Na(+)](i) handling system may differ not only between normal and diseased hearts but also regionally within a heart. To gain new insight concerning disease- and region-dependent differences in the [Na(+)](i)-regulatory system, we investigated mRNA expression of Na+ transporters, the principal determinants of [Na(+)](i). Nonischemic pressure-overloaded hypertrophy was created by suprarenal abdominal aortic constriction of 50% for 7 weeks. mRNA abundances of Na(+)-Ca(2+) exchanger (NCX1), Na(+)-H(+) exchanger (NHE1), Na(+)-K(+)-2Cl(-) exchanger (NKCC1) and Na(+), K(+)-ATPase multigene family(alpha(1), alpha(2), alpha(3), and beta(1) isoforms) were measured by the real-time quantitative polymerase chain reaction method. mRNA abundance of all transporters mediating Na(+) influx (NCX1, NHE1, and NKCC1) was significantly upregulated as compared to normal. In contrast, Na(+)-efflux-mediating transporter (Na(+), K(+)-ATPase) mRNA expression was unaltered between normal and hypertrophic hearts. Losartan, an angiotensin II AT1 receptor antagonist, significantly attenuated upregulation of Na(+)-influx-mediating transporters induced by aortic constriction. The onset of Na(+)-influx-mediating transporter upregulation occurred within 5 days following constriction. In normal and hypertrophied hearts, mRNA of all Na(+)-influx-mediating transporters was expressed in order of abundance as: apex > septum approximately free wall of left ventricles. A transmural gradient in expression was also evident in normal hearts (midcardium > endo- and epicardium), which was attenuated under hypertrophic development. Myocardial hypertrophy is associated with significant changes in the spatial distribution and expression levels of Na(+) transporters. The upregulation of Na influx transporters during hypertrophy may contribute to the remodeling process, modulate contractility and promote arrhythmias.
Yamamoto
Taku
T
Department of Cardiology and Vascular Regenerative Medicine, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan. takuy24@amber.plala.or.jp
Shirayama
Takeshi
T
Takahashi
Tomosaburo
T
Matsubara
Hiroaki
H
D000818:Animals; D002312:Cardiomyopathy, Hypertrophic / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics*; D051381:Rats; D017208:Rats, Wistar; D000254:Sodium-Potassium-Exchanging ATPase / Q000096:biosynthesis / Q000235:genetics*
D012333:RNA, Messenger; D000254:Sodium-Potassium-Exchanging ATPase