title: Metoprolol impairs resistance artery function in mice.
abstract: 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 and clenbuterol), and the myogenic response, were assessed in isolated mesenteric resistance arteries (MRAs; ∼200-μm diameter) and posterior cerebral arteries (PCAs ∼150-μm diameter). Data are presented as means ± SE with statistical significance applied at P < 0.05. Metoprolol treatment did not effect MAP but reduced heart rate and stroke volume, CO, rCBF, and brain microvascular Po(2), while concurrently increasing systemic vascular resistance (P < 0.05 for all). In isolated MRAs, metoprolol did not affect basal artery tone or the myogenic response, but it did cause 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.
authors.affiliation: Department of Anesthesia, St. Michael's Hospital, Keenan Research Centre of the Li Ka Shing Knowledge Institute, University of Toronto, Canada.
authors.forename: Mostafa H
authors.initials: MH
authors.lastname: El Beheiry
authors.forename: Scott P
authors.initials: SP
authors.lastname: Heximer
authors.forename: Julia
authors.initials: J
authors.lastname: Voigtlaender-Bolz
authors.forename: C David
authors.initials: CD
authors.lastname: Mazer
authors.forename: Kim A
authors.initials: KA
authors.lastname: Connelly
authors.forename: David F
authors.initials: DF
authors.lastname: Wilson
authors.forename: W Scott
authors.initials: WS
authors.lastname: Beattie
authors.forename: Albert K Y
authors.initials: AK
authors.lastname: Tsui
authors.forename: Hangjun
authors.initials: H
authors.lastname: Zhang
authors.forename: Kabir
authors.initials: K
authors.lastname: Golam
authors.forename: Tina
authors.initials: T
authors.lastname: Hu
authors.forename: Elaine
authors.initials: E
authors.lastname: Liu
authors.forename: Darcy
authors.initials: D
authors.lastname: Lidington
authors.forename: Steffen-Sebastian
authors.initials: SS
authors.lastname: Bolz
authors.forename: Gregory M T
authors.initials: GM
authors.lastname: Hare
mesh_terms: D058671:Adrenergic beta-1 Receptor Antagonists / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D002302:Cardiac Output / Q000187:drug effects / Q000502:physiology; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D008790:Metoprolol / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D055806:Microvessels / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D024510:Muscle Development / Q000187:drug effects / Q000502:physiology; D010100:Oxygen / Q000378:metabolism; D020769:Posterior Cerebral Artery / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism*; D013318:Stroke Volume / Q000187:drug effects / Q000502:physiology; D014655:Vascular Resistance / Q000187:drug effects* / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
chemical_list: D058671:Adrenergic beta-1 Receptor Antagonists; D000318:Adrenergic beta-Agonists; D018343:Receptors, Adrenergic, beta-2; D008790:Metoprolol; D010100:Oxygen