title: Treatment with angiotensin-(1-9) alleviates the cardiomyopathy in streptozotocin-induced diabetic rats.
abstract: Diabetic cardiomyopathy, a disorder of the heart muscle in diabetic patients, is one of the major causes of heart failure. We hypothesized that angiotensin-(1-9) [Ang-(1-9)] attenuates cardiomyopathy in streptozotocin (STZ)-induced diabetic rats. Rats were injected with a single intraperitoneal injection of STZ (55 mg/kg body weight) to induced diabetic cardiomyopathy. 4 weeks later, diabetic rats were treated with Ang-(1-9) (200 ng/kg/min), angiotensin type 2 receptor (AT2R) blocker PD123319 (100 ng/kg/min), or Mas antagonist A779 (100 ng/kg/min) for 4 weeks. Although Ang-(1-9) treatment did not affect blood glucose and insulin levels, it significantly attenuated cardiac hypertrophy, reduced cardiac fibrosis and improved ventricular function in STZ-induced diabetic rats. Ang-(1-9) treatment suppressed cardiac NADPH oxidase activity and reduced formation of reactive oxygen species. Ang-(1-9) suppressed NFκB activation and reduced myeloperoxidase (MPO) activity and mRNA levels of TNFα and IL-1β in hearts of diabetic rats. In addition, Ang-(1-9) treatment suppressed activity of ACE and reduced angiotensin II (Ang II) formation in hearts of diabetic rats. The beneficial effect of Ang-(1-9) was blunted by coadministration of PD123319 but not by coadministration of A779. Finally, it was found that Ang-(1-9) treatment could alleviate STZ-induced cardiomyopathy in a dose-dependent manner. In conclusions, Ang-(1-9) attenuates cardiac dysfunction in STZ-induced diabetic rats. The Ang-(1-9)/AT2R axis should be investigated as a novel target for treatment of type 1 diabetic cardiomyopathy.
authors: Department of Endocrinology and Metabolism, Minhang Hospital, Fudan University, Shanghai, China.
authors: Hui
authors: H
authors: Zheng
authors: Department of Neurology, Shanghai Xuhui District Dahua Hospital, Shanghai 200237, China.
authors: Su-Ying
authors: SY
authors: Pu
authors: Department of Endocrinology and Metabolism, Minhang Hospital, Fudan University, Shanghai, China.
authors: Xiao-Fang
authors: XF
authors: Fan
authors: Department of Endocrinology and Metabolism, Minhang Hospital, Fudan University, Shanghai, China.
authors: Xue-Song
authors: XS
authors: Li
authors: Department of Endocrinology and Metabolism, Minhang Hospital, Fudan University, Shanghai, China.
authors: Yu
authors: Y
authors: Zhang
authors: Department of Pharmacology, Changhai Hospital, Second Military Medical University, Shanghai, China.
authors: Jun
authors: J
authors: Yuan
authors: Department of Pharmacology, School of Pharmacy, Second Military Medical University, Shanghai, China.
authors: Yue-Fan
authors: YF
authors: Zhang
authors: Department of Endocrinology and Metabolism, Minhang Hospital, Fudan University, Shanghai, China. Electronic address: yangjl20154@outlook.com.
authors: Jia-Lin
authors: JL
authors: Yang
mesh_terms: D000803:Angiotensin I / Q000008:administration & dosage*; D000818:Animals; D009202:Cardiomyopathies / Q000188:drug therapy* / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism*; D007262:Infusions, Intravenous; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D010446:Peptide Fragments / Q000008:administration & dosage*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin; D016896:Treatment Outcome
chemical_list: D010446:Peptide Fragments; C506331:angiotensin I (1-9); D013311:Streptozocin; D000803:Angiotensin I
keywords: Angiotensin-(1-9); Diabetic cardiomyopathy; Fibrosis; Hypertrophy; Renin-angiotensin system