Abnormal amounts of intracellular calcium regulatory proteins in SHRSP.Z-Lepr(fa)/IzmDmcr rats with metabolic syndrome and cardiac dysfunction

作者：Kagota Satomi^*; Maruyama Kana; Tada Yukari; Wakuda Hirokazu; Nakamura Kazuki; Kunitomo Masaru; Shinozuka Kazumasa

来源：Canadian Journal of Physiology and Pharmacology, 2013, 91(2): 124-133.

DOI：10.1139/cjpp-2012-0226

• cardiac diastolic function
• hypertension
• metabolic syndrome
• obesity
• phospholamban
• sarcoplasmic reticulum Ca2+-ATPase
• telmisartan

Metabolic syndrome is known to increase the risk of abnormal cardiac structure and function, which are considered to contribute to increased incidence of cardiovascular disease and mortality. We previously demonstrated that ventricular hypertrophy and diastolic dysfunction occur in SHRSP. Z-Lepr(fa)/IzmDmcr (SHRSP fatty) rats with metabolic syndrome. The aim of this study was to investigate the possible mechanisms underlying abnormal heart function in SHRSP fatty rats. The amount of sarcoplasmic reticulum Ca2+-ATPase (SERCA) 2a, phospholamban (PLB) protein, and Ser(16)-phosphorylated PLB was decreased in cardiomyocytes from SHRSP fatty rats compared with those from control Wistar-Kyoto rats at 18 weeks of age, and the PLB-to-SERCA2a ratio was increased. Left ventricular developed pressure was unchanged, and coronary flow rate and maximum rate of left ventricular pressure decline (-dP/dt) was decreased in SHRSP fatty rats. Treatment with telmisartan reversed the abnormalities of PLB amount, coronary flow rate, and -dP/dt in SHRSP fatty rats. These results indicate that abnormal amounts of intracellular Ca2+ regulatory proteins in cardiomyocytes, leading to reduced intracellular Ca2+ reuptake into the sarcoplasmic reticulum, may play a role in the diastolic dysfunction in SHRSP fatty rats and that these effects are partially related to decreased coronary circulation. Telmisartan may be beneficial in protecting against disturbances in cardiac function associated with metabolic syndrome.

• 出版日期2013-2