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Metoprolol Impairs Mesenteric and Posterior Cerebral Artery Function in Mice

Background/Rationale: In addition to their established cardioprotective role, β-adrenergic antagonists also increase the risk of stroke and mortality. We propose that a vascular mechanism could contribute to cerebral tissue ischemia in β-blocked patients.
Methods: Cardiac output (CO), mean arterial pressure (MAP) and microvascular brain oxygen tension (PBrmvO2) were measured in anesthesized mice treated with metoprolol (3mg•kg-1, i.v.). Dose-response curves (DRCs) for adrenergic-agonists were generated in mesenteric resistance arteries (MRAs; isoproterenol, clenbuterol) and posterior cerebral arteries (PCAs; phenylephrine, isoproterenol) before and after metoprolol treatment.
Results: Metoprolol reduced CO, maintained MAP and increased systemic vascular resistance (SVR) resulting in a decreased PBrmvO2 in mice. Metoprolol attenuated β-adrenergic mediated vasodilation in both MRAs and PCAs.
Conclusions: Metoprolol reduced brain perfusion in mice. A decrease in CO contributed however, metoprolol also inhibited β-adrenergic vasodilation of mesenteric and cerebral arteries. This provides evidence in support of a vascular mechanism for cerebral ischemia in β-blocked patients.

Identiferoai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/25561
Date31 December 2010
CreatorsEl Beheiry, Mostafa Hossam
ContributorsHare, Gregory, Bolz, Steffen Sebastian
Source SetsUniversity of Toronto
Languageen_ca
Detected LanguageEnglish
TypeThesis

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