Infarct Size-Reducing Effect of Ischemic Preconditioning Is Related to α1b-Adrenoceptors But Not to α1a-Adrenoceptors in Rabbits

Kariya, Takehiko; Minatoguchi, Shinya; Ohno, Tsuzuki; Yamashita, Kazuya; Uno, Yoshihiro; Arai, M.; Koshiji, Masatoshi; Fujiwara, Takako; Fujiwara, Hisayoshi

doi:10.1097/00005344-199710000-00006

Cited by 25 publications

(24 citation statements)

References 35 publications

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“…α1-Antagonists have negative effects on adaptive cardiac processes in vitro and in animal models in vivo [132, 153–155] (Table 3), supporting the data from pharmacology gain of function (Table 1). However, the pharmacologic tools can have nonspecific effects, and are inadequate to distinguish α1-subtypes in vivo.…”

Section: Evidence From α1-ar Loss Of Function In Animal Models (Table 3)supporting

confidence: 60%

Alpha-1-adrenergic receptors: Targets for agonist drugs to treat heart failure

Jensen

OʼConnell

Simpson

2011

Journal of Molecular and Cellular Cardiology

109

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Evidence from cell, animal, and human studies demonstrates that α1-adrenergic receptors mediate adaptive and protective effects in the heart. These effects may be particularly important in chronic heart failure, when catecholamine levels are elevated and β-adrenergic receptors are down regulated and dysfunctional. This review summarizes these data and proposes that selectively activating α1-adrenergic receptors in the heart may represent a novel and effective way to treat heart failure. Keywordsalpha-1-adrenergic receptors; cardiac myocytes; heart failure; drug development Description of α1-ARsThe neurohormonal alterations of heart failure (HF) are characterized by marked elevations in sympathetic catecholamines, norepinephrine (NE) and epinephrine (EPI) [1]. NE and EPI activate two main classes of myocardial adrenergic receptors (ARs), alpha-1-ARs (α1-ARs) and beta-ARs (β-ARs). The most abundant cardiac AR is the β1-AR, though there are also smaller but functionally important populations of β2-and α1-ARs. All ARs are prototypical G-protein coupled receptors (GPCRs) with seven transmembrane domains, though they differentially activate Gα subunits: β-ARs couple predominantly to Gs, and α1-ARs to Gq, although β2-and α1-ARs can also couple to Gi.Correspondence: Paul C. Simpson MD, VA Medical Center (111-C-8), 4150 Clement St., San Francisco, CA 94121 USA, Phone: (415) 221-4810 x3200, FAX: (415) 379-5570, paul.simpson@ucsf.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. DISCLOSURESA patent application is submitted to use α1-agonist compounds as treatment. NIH Public Access NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptAcute activation of β1-ARs increases heart rate and myocardial contractility. However excessive chronic stimulation of cardiac β1-ARs, as with elevated catecholamines in HF, mediates harmful processes, including cell death, fibrosis, and adverse remodeling [2][3][4][5][6][7][8][9]. Interestingly, recent investigations suggest that myocardial β2-ARs might mitigate the harm associated with chronic β1-AR activation (article by Talan et al in this issue, and [10,11]). Nevertheless, drugs that block the activation of β-ARs (β-blockers) reduce HF morbidity and mortality and have become a cornerstone of HF therapy [12]. α1-ARs in the heart have been the subject of less intensive investigation, but multiple lines of evidence define adaptive and protective roles for cardiac α1-ARs (Tables 1-3) that contrast sharply with the toxic effects of excessive chronic β-AR activation [9].α1-ARs exist as three distinct molecular subtypes, na...

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Section: Evidence From α1-ar Loss Of Function In Animal Models (Table 3)supporting

confidence: 60%

Alpha-1-adrenergic receptors: Targets for agonist drugs to treat heart failure

Jensen

OʼConnell

Simpson

2011

Journal of Molecular and Cellular Cardiology

109

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“…Consistent with our data, Gao et al [24] found that expression of CAM a 1B -ARs in the heart-targeted transgenic mouse does not protect the heart from ischemic injury. However, others have reported that ischemic preconditioning of rat and rabbit hearts is mediated by a 1B -ARs [25][26][27]. It is possible that the a 1 -AR subtype that mediates ischemic preconditioning is different in the mouse heart than in rabbit or rat hearts.…”

Section: Discussionmentioning

confidence: 99%

?- but not ?-adrenergic receptors precondition the ischemic heart by a staurosporine-sensitive, chelerythrine-insensitive mechanism

Rorabaugh

Ross

Gaivin

et al. 2005

Cardiovascular Research

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“…Besides the inhibition of glycogenolysis, there are several mechanisms for PC, such as the activation of adenosine receptors, 6 1b-adrenoceptors, 7 bradykinin B2 receptors 8 and oxyradicals, 9 that can independently activate protein kinase C and the opening of the mitochondrial KATP channel. Therefore, these mechanisms might also contribute to the marked effect of the combination of NMDN and PC.…”

Section: Discussionmentioning

confidence: 99%