title: Early administration of nifedipine protects against angiotensin II-induced cardiomyocyte hypertrophy through regulating CaMKII-SERCA2a pathway and apoptosis in rat cardiomyocytes.
abstract: The calcium channel blocker (CCB), nifedipine, is a more effective treatment for early- than late-stage cardiac hypertrophy. We investigated the effects of early- and late-stage nifedipine administration on calcium homeostasis, CaMKII (Ca(2+) /calmodulin-dependent protein kinase II) activity and apoptosis of cardiomyocytes under hypertrophic stimulation with angiotensin II (AngII). Primary rat cardiomyocytes were divided into five treatment groups: AK, AngII plus the CaMKII inhibitor, KN-93; AN-1 (early-stage), AngII plus nifedipine × 48 h; AN-2 (late-stage), AngII × 48 h, then AngII plus nifedipine × 48 h; C, untreated; and A, AngII × 48 h. The t1/2β [time required for intracellular Ca(2+) concentration ([Ca(2+) ]i) to decline to one half of the peak value] decreased; however, CaMKII and SERCA2a (sarcoplasmic reticulum Ca(2+) -ATPase 2a) activities increased in the AN-1 group compared with the AK group. In the AN-2 group compared with the AN-1 group, CaMKII activity, t1/2α [time required for [Ca(2+) ]i to increase from the bottom to one half of peak value], t1/2β, and apoptosis increased. These results indicate that the timing of CCB administration affects the calcium concentration and apoptosis of hypertrophic cardiomyocytes through the CaMKII-SERCA2a signalling pathway, thereby influencing the drug's protective activity against cardiomyocyte hypertrophy.
authors.affiliation: Department of Cardiology, the Second Hospital of Shandong University, Shandong, Jinan, 250033, China.
authors.forename: Ji
authors.initials: J
authors.lastname: Luo
authors.affiliation: Basic Research Institute of Medical Sciences in Shandong, Shandong, Jinan, 250012, China.
authors.forename: Wei-dong
authors.initials: WD
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, the Second Hospital of Shandong University, Shandong, Jinan, 250033, China.
authors.forename: Yi-meng
authors.initials: YM
authors.lastname: Du
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism*; D006332:Cardiomegaly / Q000139:chemically induced* / Q000188:drug therapy* / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D009543:Nifedipine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000804:Angiotensin II; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D009543:Nifedipine
keywords: CaMKII; KN-93; SERCA2a; cardiomyocyte hypertrophy; nifedipine