title: The effects of angiotensin II signaling pathway in the systolic response to acute stretch in the normal and ischemic myocardium.
abstract: 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% Lmax 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(+)/Ca(2+)-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.
authors.affiliation: Department of Physiology and Cardiothoracic Surgery, Faculty of Medicine, University of Porto, Porto, Portugal.
authors.forename: João Sérgio
authors.initials: JS
authors.lastname: Neves
authors.forename: Ricardo
authors.initials: R
authors.lastname: Castro-Ferreira
authors.forename: Ricardo
authors.initials: R
authors.lastname: Ladeiras-Lopes
authors.forename: Manuel
authors.initials: M
authors.lastname: Neiva-Sousa
authors.forename: André M
authors.initials: AM
authors.lastname: Leite-Moreira
authors.forename: João
authors.initials: J
authors.lastname: Almeida-Coelho
authors.forename: Ricardo
authors.initials: R
authors.lastname: Fontes-Carvalho
authors.forename: João
authors.initials: J
authors.lastname: Ferreira-Martins
authors.forename: Adelino F
authors.initials: AF
authors.lastname: Leite-Moreira
mesh_terms: D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D001794:Blood Pressure; D008297:Male; D009200:Myocardial Contraction / Q000502:physiology*; D017202:Myocardial Ischemia / Q000378:metabolism* / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism; D011817:Rabbits; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D044139:Receptor, Angiotensin, Type 2 / Q000378:metabolism; D015398:Signal Transduction; D019831:Sodium-Calcium Exchanger / Q000378:metabolism; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism; D013314:Stress, Mechanical; D013312:Stress, Physiological
chemical_list: D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D019831:Sodium-Calcium Exchanger; D017923:Sodium-Hydrogen Exchangers; D000804:Angiotensin II; D011493:Protein Kinase C
keywords: Angiotensin II; Frank–Starling mechanism; Ischemia; Myocardial stretch; Slow force response