title: Abnormal amounts of intracellular calcium regulatory proteins in SHRSP.Z-Lepr(fa)/IzmDmcr rats with metabolic syndrome and cardiac dysfunction.
abstract: 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 Ca(2+)-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 Ca(2+) regulatory proteins in cardiomyocytes, leading to reduced intracellular Ca(2+) 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.
authors: Department of Pharmacology II, School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women's University, Nishinomiya 663-8179, Japan. skagota@mukogawa-u.ac.jp
authors: Satomi
authors: S
authors: Kagota
authors: Kana
authors: K
authors: Maruyama
authors: Yukari
authors: Y
authors: Tada
authors: Hirokazu
authors: H
authors: Wakuda
authors: Kazuki
authors: K
authors: Nakamura
authors: Masaru
authors: M
authors: Kunitomo
authors: Kazumasa
authors: K
authors: Shinozuka
mesh_terms: D000818:Animals; D001562:Benzimidazoles / Q000008:administration & dosage / Q000627:therapeutic use; D001565:Benzoates / Q000008:administration & dosage / Q000627:therapeutic use; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D002784:Cholesterol / Q000097:blood; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology; D003971:Diastole / Q000187:drug effects; D004195:Disease Models, Animal; D006334:Heart Function Tests; D007328:Insulin / Q000097:blood; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D011919:Rats, Inbred Strains; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000378:metabolism*; D012694:Serine / Q000378:metabolism; D000077333:Telmisartan; D014280:Triglycerides / Q000097:blood; D018754:Ventricular Dysfunction / Q000097:blood / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D016277:Ventricular Function, Left / Q000187:drug effects / Q000502:physiology; D000099211:Phospholamban
chemical_list: D001562:Benzimidazoles; D001565:Benzoates; D001786:Blood Glucose; D002118:Calcium; D002135:Calcium-Binding Proteins; D002784:Cholesterol; D007328:Insulin; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D012694:Serine; D000077333:Telmisartan; D014280:Triglycerides; D000099211:Phospholamban; C506948:Atp2a2 protein, rat