The effects of angiotensin II signaling pathway in the systolic response to acute stretch in the normal and ischemic myocardium

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• 作者：Jo?o S¨¦rgio Neves ; Ricardo Castro-Ferreira ; Ricardo Ladeiras-Lopes ; Manuel Neiva-Sousa ; Andr¨¦ M. Leite-Moreira ; Jo?o Almeida-Coelho ; Ricardo Fontes-Carvalho ; Jo?o Ferreira-Martins ; Adelino F. Leite-Moreira
• 关键词：Angiotensin II ; Myocardial stretch ; Frank&ndash ; Starling mechanism ; Slow force response ; Ischemia
• 刊名：Peptides
• 出版年：2013
• 出版时间：September, 2013
• 年：2013
• 卷：47
• 期：Complete
• 页码：77-84
• 全文大小：1259 K

文摘

Acute myocardial stretch elicits a biphasic increase in contractility: an immediate increase, known as Frank-Starling mechanism (FSM), followed by a progressive increase, regarded as slow force response (SFR). In this study, we characterized the contractile response to acute stretch from 92 to 100 % L_max in rabbit papillary muscles (n = 86) under normoxic and ischemic conditions, and its modulation by angiotensin II signaling pathway. Under normoxia, the FSM was independent of Na⁺/H⁺-exchanger, reverse mode of Na⁺/Ca²⁺-exchanger (r-NCX), AT1 receptor, AT2 receptor and PKC. Regarding the SFR, it was mediated by AT1 receptor activation and its downstream effectors PKC, Na⁺/H⁺-exchanger and r-NCX. Ischemia negatively impacted on the FSM and abolished the SFR, with the muscles exhibiting a time-dependent decline in contractility. Under ischemic conditions, FSM was not influenced by AT1 and AT2 receptors or PKC activation. AT1 receptor antagonism rescued the progressive deterioration in contractility, an effect partially dependent on AT2 receptor activation.