Metoprolol impairs resistance artery function in mice

J Appl Physiol (1985). 2011 Oct;111(4):1125-33. doi: 10.1152/japplphysiol.01340.2010. Epub 2011 Jul 28.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-1 Receptor Antagonists / pharmacology
  • Adrenergic beta-Agonists / pharmacology
  • Animals
  • Blood Pressure / drug effects
  • Blood Pressure / physiology
  • Brain / blood supply
  • Brain / drug effects
  • Brain / metabolism
  • Brain / physiology
  • Cardiac Output / drug effects
  • Cardiac Output / physiology
  • Cerebrovascular Circulation / drug effects
  • Cerebrovascular Circulation / physiology
  • Heart Rate / drug effects
  • Heart Rate / physiology
  • Mesenteric Arteries / drug effects*
  • Mesenteric Arteries / metabolism
  • Mesenteric Arteries / physiology
  • Metoprolol / pharmacology*
  • Mice
  • Mice, Inbred C57BL
  • Microvessels / drug effects
  • Microvessels / metabolism
  • Microvessels / physiology
  • Muscle Development / drug effects
  • Muscle Development / physiology
  • Oxygen / metabolism
  • Posterior Cerebral Artery / drug effects
  • Posterior Cerebral Artery / metabolism
  • Posterior Cerebral Artery / physiology
  • Receptors, Adrenergic, beta-2 / metabolism*
  • Stroke Volume / drug effects
  • Stroke Volume / physiology
  • Vascular Resistance / drug effects*
  • Vascular Resistance / physiology
  • Vasodilation / drug effects
  • Vasodilation / physiology

Substances

  • Adrenergic beta-1 Receptor Antagonists
  • Adrenergic beta-Agonists
  • Receptors, Adrenergic, beta-2
  • Metoprolol
  • Oxygen