Background: Cardiac surgery and cardiopulmonary bypass (CPB) are associated with alterations in blood pressure in the perioperative period, which if uncontrolled, can result in end organ damage or dysfunction. Microvessels, significant contributors to blood pressure, both in the myocardium and peripheral skeletal muscle, have diminished responsiveness to major mediators of vascular tone, including thromboxane and serotonin after CPB. Responsiveness of these vessels to β-adrenergic stimulation, a major mediator of vascular tone, has not yet been studied. Here, we will investigate the role of β-adrenergic receptors in vascular tone regulation in human skeletal muscle microvessels before and after CPB.Methods: Skeletal muscle microvessels were isolated from patients undergoing cardiac surgery before and after CPB. Vessels were exposed in an ex-vivo model to the β-adrenergic agonist isoproterenol, or the direct adenylyl cyclase activator, forskolin, and the selective β-receptor antagonist ICI18.551 hydrochloride plus isoproterenol. Immunofluorescence of β-receptors and western blotting were also performed.Results: Microvessels showed diminished responsiveness to isoproterenol (10 −6 -10 −4 M) after CPB (n = 8/group, p = 0.01). Pretreatment with the selective β−2 blocker ICI18.551 (10-6 M) prevented isoproterenol-induced microvascular relaxation (p = 0.001). Forskolin-induced relaxation response was also significantly diminished post CPB (n = 4/group, p < 0.05 vs. pre CPB). No significant changes in the total protein expression of β−1, β−2 and β−3 receptors were detected by western blotting or immunofluorescence.