{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T11:48:36Z","timestamp":1773661716417,"version":"3.50.1"},"reference-count":29,"publisher":"American Physiological Society","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2011,11]]},"abstract":"<jats:p> Impaired Ca<jats:sup>2+<\/jats:sup> handling is one of the main characteristics in heart failure patients. Recently, we reported abnormal expressions of Ca<jats:sup>2+<\/jats:sup>-handling proteins in isoproterenol (ISO)-induced hypertrophied rat hearts. On the other hand, Na<jats:sup>+<\/jats:sup>\/H<jats:sup>+<\/jats:sup> exchanger (NHE)-1 inhibitor has been demonstrated to exert beneficial effects in ischemic-reperfusion injury and in the development of cardiac remodeling. The aims of the present study are to investigate the role of NHE-1 on Ca<jats:sup>2+<\/jats:sup> handling and development of cardiac hypertrophy in ISO-infused rats. Male Wistar rats were randomly divided into vehicle [control (CTL)] and ISO groups without or with pretreatment with a selective NHE-1 inhibitor, BIIB-723. ISO infusion for 1 wk significantly increased the ratios of heart to body weight and left ventricle (LV) to body weight and collagen accumulation. All of these increases were antagonized by coadministration with BIIB-723. The ISO-induced significant increase in LV wall thickness was suppressed significantly ( P &lt; 0.05) by BIIB-723. ISO-induced decreases in cardiac stroke volume and a total mechanical energy per beat index, systolic pressure-volume area at midrange LV volume, were normalized by BIIB-723. The markedly higher expression of NHE-1 protein in the ISO group than that in CTL group was suppressed ( P &lt; 0.05) by BIIB-723. Surprisingly, ISO induced downregulation of the important Ca<jats:sup>2+<\/jats:sup>-handling protein sarcoplasmic reticulum Ca<jats:sup>2+<\/jats:sup>-ATPase 2a, the expression of which was also normalized by BIIB-723 without changes in phosphorylated phospholamban (PLB)\/PLB expression. We conclude that NHE-1 contributes to ISO-induced abnormal Ca<jats:sup>2+<\/jats:sup> handling associated with cardiac hypertrophy. Inhibition of NHE-1 ameliorates cardiac Ca<jats:sup>2+<\/jats:sup>-handling impairment and prevents the development of cardiac dysfunction in ISO-infused rats. <\/jats:p>","DOI":"10.1152\/ajpheart.00483.2011","type":"journal-article","created":{"date-parts":[[2011,8,22]],"date-time":"2011-08-22T21:44:32Z","timestamp":1314049472000},"page":"H2154-H2160","source":"Crossref","is-referenced-by-count":21,"title":["NHE-1 participates in isoproterenol-induced downregulation of SERCA2a and development of cardiac remodeling in rat hearts"],"prefix":"10.1152","volume":"301","author":[{"given":"Munetaka","family":"Shibata","sequence":"first","affiliation":[{"name":"Department of Physiology II, Nara Medical University School of Medicine, Kashihara, Nara, Japan; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daisuke","family":"Takeshita","sequence":"additional","affiliation":[{"name":"Department of Physiology II, Nara Medical University School of Medicine, Kashihara, Nara, Japan; 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