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Altered expression of Na+ transporters at the mRNA level in rat normal and hypertrophic myocardium

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Abstract

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+-Ca2+ exchanger (NCX1), Na+-H+ exchanger (NHE1), Na+-K+-2Cl− exchanger (NKCC1) and Na+, K+-ATPase multigene family(α1, α2, α3, and β1 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 ∼ 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.

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Authors and Affiliations

  1. Department of Cardiology and Vascular Regenerative Medicine, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan

    Taku Yamamoto, Takeshi Shirayama, Tomosaburo Takahashi & Hiroaki Matsubara

  2. Department of Cardiology, Aiseikai Yamashina Hospital, Takehana Yonchono-cho, Yamashina-ku, Kyoto, 607-8086, Japan

    Taku Yamamoto

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  1. Taku Yamamoto
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  2. Takeshi Shirayama
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  3. Tomosaburo Takahashi
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  4. Hiroaki Matsubara
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Correspondence to Taku Yamamoto.

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Yamamoto, T., Shirayama, T., Takahashi, T. et al. Altered expression of Na+ transporters at the mRNA level in rat normal and hypertrophic myocardium. Heart Vessels 24, 54–62 (2009). https://doi.org/10.1007/s00380-008-1071-8

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  • DOI: https://doi.org/10.1007/s00380-008-1071-8

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