1. Cellular basis of angiotensin-(1-7)-induced augmentation of left ventricular functional performance in heart failure.
- Author
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Zhang, Xiaowei, Cheng, Heng-Jie, Zhou, Peng, Kitzman, Dalane W., Ferrario, Carlos M., Li, Wei-Min, and Cheng, Che Ping
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ANGIOTENSIN II , *HEART failure treatment , *HEART physiology , *LEFT heart ventricle , *BRADYKININ , *LABORATORY rats , *THERAPEUTICS - Abstract
Background Angiotensin-(1-7) [Ang-(1-7)] exhibits cardiovascular effects opposite those of angiotensin II (Ang II), thus providing protection against heart disease. However, how Ang-(1-7) imparts cardioprotection is unclear, and its direct cardiac effects are controversial. Whether heart failure (HF) alters cardiac contractile responses to Ang-(1-7) remains undetermined. We tested the hypothesis that in HF, Ang-(1-7) may produce positive modulation on [Ca 2 + ] i regulation, enhancing left ventricular (LV) and myocyte contraction and relaxation via Ang-(1-7) Mas receptor coupled with nitric oxide (NO)/bradykinin (BK)-mediated mechanism. Methods and results We measured LV contractility changes after Ang-(1-7) (650 ng/kg, iv) and compared myocyte functional and [Ca 2 + ] i transient ([Ca 2 + ] iT ) responses to Ang-(1-7) superfusion in 24 normal rats and 34 rats with isoproterenol-induced HF (3 months after 170 mg/kg, s.q. for 2 days). To assess the mechanisms of altered HF responses to Ang-(1-7), subsets of HF myocytes were pretreated to inhibit NO synthase (L-NAME), BK (HOE-140), and Mas receptor (A-779) followed with Ang-(1-7). In normal rats, Ang-(1-7) produced no significant changes in LV and myocyte function. In HF rats, Ang-(1-7) significantly augmented LV contractility and relaxation with increased E ES (51%), but decreased τ compared to baseline. Ang-(1-7) also significantly increased myocyte contraction (dL/dt max , 30%), relaxation (dR/dt max , 41%), and [Ca 2 + ] iT . L-NAME increased, HOE-140 decreased, and A-779 prevented HF myocyte contractile responses to Ang-(1-7). Conclusions In a rat model of HF, Ang-(1-7) increases [Ca 2 + ] iT , and produces positive inotropic and lusitropic effects in the LV and myocytes. These effects are mediated by the Mas receptor and involve activation of NO/BK pathways. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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