| Metoprolol impairs resistance artery function in mice. | |
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MedLine Citation:
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PMID: 21799135 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Acute β-blockade with metoprolol has been associated with increased mortality by undefined mechanisms. Since metoprolol is a relatively high affinity blocker of β(2) adrenoreceptors, we hypothesized that some of the increased mortality associated with its use may be due to its abrogation of β(2)-adrenoreceptor-mediated vasodilation of microvessels in different vascular beds. Cardiac output (CO, pressure volume loops), mean arterial pressure (MAP), relative cerebral blood flow (rCBF, laser Doppler) and microvascular brain tissue PO(2) (G2 oxyphor) were measured in anesthetized mice before and after acute treatment with metoprolol (3 mg/kg iv). The vasodilatory dose responses to β-adrenergic agonists (isoproterenol, clenbuterol), and the myogenic response, were assessed in isolated mesenteric resistance arteries (MRA) (~200μm diameter) and posterior cerebral arteries (PCA) (~150μm diameter). Data are presented as mean ± SEM with statistical significance applied at p<0.05. Metoprolol treatment did not effect MAP but reduced heart rate (HR) and stroke volume (SV), CO, rCBF and brain microvascular PO(2), while concurrently increasing systemic vascular resistance (SVR) (p<0.05 for all). In isolated MRAs, metoprolol did not affect basal artery tone, or the myogenic response, but did caused a dose dependent impairment of isoproterenol and clenbuterol induced vasodilation. In isolated PCAs, metoprolol (50 μM) impaired maximal vasodilation in response to isoproterenol. These data support the hypothesis that acute administration of metoprolol can reduce tissue oxygen delivery by impairing the vasodilatory response to β(2)-adrenergic agonists. This mechanism may contribute to the observed increase in mortality associated with acute administration of metoprolol in perioperative patients. |
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Authors:
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Mostafa H El Beheiry; Scott P Heximer; Julia Voigtlaender-Bolz; C David Mazer; Kim A Connelly; David F Wilson; W Scott Beattie; Albert K Y Tsui; Hangjun Zhang; Kabir Golam; Tina Hu; Elaine Liu; Darcy Lidington; Steffen-Sebastian Bolz; Gregory M T Hare |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-7-28 |
Journal Detail:
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Title: Journal of applied physiology (Bethesda, Md. : 1985) Volume: - ISSN: 1522-1601 ISO Abbreviation: - Publication Date: 2011 Jul |
Date Detail:
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Created Date: 2011-7-29 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8502536 Medline TA: J Appl Physiol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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1University of Toronto. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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