Skeletal muscle microvasculature response to β-adrenergic stimuli is diminished with cardiac surgery
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- Brown University
Background: Cardiac surgery and cardiopulmonary bypass 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 cardiopulmonary bypass. Responsiveness of these vessels to β-adrenergic stimulation, a major mediator of vascular tone, has not yet been studied. In this report, we investigated the role of β-adrenergic receptors in vascular tone regulation in human skeletal muscle microvessels before and after β-adrenergic stimulation. Methods: Skeletal muscle microvessels were isolated from patients undergoing cardiac surgery before and after cardiopulmonary bypass. 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 to 10–4M) after cardiopulmonary bypass (n = 8/group, P =.01). Pretreatment with the selective β-2 blocker ICI18.551 (10–6M) prevented isoproterenol-induced microvascular relaxation (P =.001). Forskolin-induced relaxation response was also significantly diminished after cardiopulmonary bypass (n = 4/group, P <.05 versus before cardiopulmonary bypass). No significant changes in the total protein expression of β-1, β-2, and β-3 receptors were detected by western blotting or immunofluorescence. Conclusion: Microvessels isolated from human skeletal muscle show diminished responsiveness to isoproterenol and its downstream activator forskolin after cardiopulmonary bypass, suggesting there is an alteration in β-adrenergic receptor responsive in adenylate cyclase. The relaxation response to isoproterenol was via activation β-2 receptors without changes in β-adrenergic receptor abundance.