Objective: We have previously demonstrated that metoprolol, a common clinically used b₁-adrenergic receptor blocker causes a significant reduction in cerebral tissue oxygen tension in acutely anemic rats. This effect may be compounded by an impairment of b-adrenergic mediated vasodilation in addition to cardiac output depression. We sought to determine if metoprolol impairs resistance artery function. Methods: Isolated mouse mesenteric resistance arteries (MRAs) were mounted to a pressure myograph in MOPS salt solution and warmed to 37°C at a transmural pressure of 60mmHg. Acute changes in diameter were measured. Dose-response curves of the non-selective b-agonist isoproterenol (ISO; 0.3mM-300mM) and the selective b₂-agonist clenbuterol (CBL; 0.3mM-300mM) were generated in MRAs preconstricted with 1mM phenylephrine (PE) before (control) and after 30min incubation of 5, 10 or 50mM metoprolol. Data presented as mean±SD. Results: The degree of preconstriction was not different before or after incubation with all concentrations of metoprolol. Metoprolol caused a significant right shift in the ISO dose-response curve following incubation at 50mM (LogEC50= -4.0±0.2 vs -4.5±0.06, n=5, p<0.01) but not at 5 and 10mM (n=7). The maximal dilation induced by the highest dose of ISO was significantly lower in 50mM metoprolol (41±5.9% vs 60±5.8%, n=5, p<0.01). This effect was not observed after 5 and 10mM incubations. At 50mM, metoprolol did not affect the CBL dose-response curve (n=4). Preliminary data in mouse posterior cerebral arteries suggests increased sensitivity to ISO (LogEC50= -6.5±0.4, n=4) and inhibition of the ISO dose-response at 50mM metoprolol (n=1). Conclusions: These results suggest that metoprolol inhibits b₁-adrenergic mediated vasodilation in MRAs. This may contribute to a mechanism of organ ischemia with b-blockade observed in both animals and patients.