title: Cardioprotective effects of oxymatrine on isoproterenol-induced heart failure via regulation of DDAH/ADMA metabolism pathway in rats.
abstract: The present study was designed to investigate whether oxymatrine could attenuate isoproterenol-induced heart failure via regulation of asymmetric dimethylarginine (ADMA) metabolism in rats. Heart failure model was established by once daily subcutaneous injection of isoproterenol (5 mg/kg/d) to rats for 7 days. Simultaneously, oral administration of oxymatrine (25, 50 and 100 mg/kg/d) was started from day 1 to day 7, or with vehicle as corresponding controls. After continuous preventive administration of oxymatrine for 7 days, significant isoproterenol-induced heart failure characterized by hypertrophy and dysfunction of left ventricle, and elevation of brain natruretic peptide (BNP, a heart failure biomarker) and cardiac troponin I (cTn-I, a cardiac injury biomarker) was observed. Preventive oxymatrine significantly ameliorated the cardiac hypertrophy, improved the left ventricular dysfunction and reduced the increased BNP and cTn-I in serum of isoproterenol-treated rats. And obvious changes with decrease of systolic blood pressure and increase of heart rate were present in isoproterenol group and normalized by oxymatrine. Besides, prevention with oxymatrine significantly up-regulated the dimethylarginine dimethylaminohydrolase 2 (DDAH2) expression, which was followed by decreased serum ADMA, but it had no effect on protein arginine methyltransferase1 (PRMT1) expression that is up-regulated in isoproterenol-induced heart failure rats. These results manifested that preventive oxymatrine could ameliorate the hypertrophy and dysfunction of left ventricle of rats with heart failure, which is attributed to modulation of DDAH/ADMA metabolism pathway by oxymatrine.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.forename: Yansheng Kang
authors.initials: YK
authors.lastname: Liu
authors.forename: Jingjing
authors.initials: J
authors.lastname: Liu
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Wang
authors.forename: Qingbin
authors.initials: Q
authors.lastname: Xu
authors.forename: Yilei
authors.initials: Y
authors.lastname: Wang
authors.forename: Xiaoya
authors.initials: X
authors.lastname: Xu
authors.forename: Guidong
authors.initials: G
authors.lastname: Dai
mesh_terms: D000470:Alkaloids / Q000494:pharmacology*; D000581:Amidohydrolases / Q000378:metabolism*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004195:Disease Models, Animal; D005260:Female; D006333:Heart Failure / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D006439:Hemodynamics / Q000187:drug effects; D007545:Isoproterenol / Q000633:toxicity; D008297:Male; D053858:Metabolic Networks and Pathways / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D020097:Natriuretic Peptide, Brain / Q000097:blood; D009929:Organ Size / Q000187:drug effects; D011484:Protein-Arginine N-Methyltransferases / Q000378:metabolism; D011807:Quinolizines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019210:Troponin I / Q000097:blood; D000093842:Matrines
chemical_list: D000470:Alkaloids; D000581:Amidohydrolases; D001120:Arginine; D002316:Cardiotonic Agents; D007545:Isoproterenol; D020097:Natriuretic Peptide, Brain; D011484:Protein-Arginine N-Methyltransferases; D011807:Quinolizines; D019210:Troponin I; C018524:N,N-dimethylarginine; C037573:oxymatrine; D000093842:Matrines; C541817:PRMT1 protein, rat; C059999:dimethylargininase