Mechanism of cardiac hypertrophy induced by activation of Na+/H+ exchanger

• Published in: Japanese Journal of Pharmacology 1998, Vol.76 (suppl.1), p.80-80
• Main Authors: Hayasaki, Yoko, Kitano, Yoshinori, Iwasaki, Takanori, Shimamura, Toshitake, Nava, Noriyuki, Iwaki, Kazumi, Nakajima, Masatoshi
• Format: Article
• Language: English
• ISSN: 0021-5198; 1347-3506
• DOI: 10.1016/S0021-5198(19)40441-1

To investigate the contribution of Na^+ /H^+ exchanger in cardiac hypertrophy, we examined the signal mechanism of Na^+ influx via activation of Na^+ /H^+ exchanger in cultured neonatal rat cardiac myocytes. Phorbor 12-myristate 13-acetate (PMA, 100 nM) increased protein synthesis and β-myosin heavy chain (MHC) protein content, and these effects were inhibited by HOE694 (1μM), an inhibitor of the Na^+ /H^+ exchanger. Veratridine and ouabain also caused increases in protein synthesis and β-MHC protein content. These effects were abolished by the protein kinase C (PKC) inhibitor staurosporine. Next, we examined the PKC isozymes activated by PMA and veratridine using immunoblot analysis. PMA (100 nM) increased α-, δ- and ε-PKC in the particulate fraction of myocytes, while HOE694 (1μM) significantly inhibited the translocation of only δ- and ε-PKC. Veratridine (100 μM) led to increase δ- and ε-PKC in the particulate fraction, but no change in α-PKC. These effects were not affected by HOE694 (1μM). In summary, these results suggest that Na^+ influx via activation of the Na^+ /H^+ exchanger activates δ- and ε-PKC. Thus, activation of δ and ε-PKC isozymes appears to be involved in the signal mechanism of the hypertrophic response in myocytes.