Peripheral vascular effects of beta-3 adrenergic receptor stimulation in conscious dogs

To characterize the physiological function of the beta-3 adrenergic receptor subtype in vivo, the effects of a beta-3 adrenergic receptor agonist, BRL37344, were examined on systemic hemodynamics and regional blood flow distribution. They were compared with beta-1 or beta-2 adrenergic receptor stimulation using isoproterenol (ISO) in conscious dogs instrumented with aortic and left atrial catheters and ascending aortic flow probes. ISO, at a dose of 0.4 μg/kg/min i.v., reduced mean arterial pressure by 7 ± 3% and increased total peripheral conductance by 145 ± 12% and heart rate by 109 ± 10%. BRL37344, at a dose of 8.3 μg/kg i.v., reduced mean arterial pressure by 9 ± 4% and increased total peripheral conductance by 91 ± 3% and heart rate by 63 ± 5%. In the presence of selective beta-1 adrenergic receptor blockade with atenolol, ISO decreased mean arterial pressure by 20 ± 5% and increased total peripheral conductance by 140 ± 26% and heart rate by 60 ± 12%. After combined beta-1 and beta-2 adrenergic receptor blockade with propranolol, ISO induced no significant effects. By contrast, after propranolol, BRL37344 still reduced mean arterial pressure by 13 ± 2% and increased total peripheral conductance by 109 ± 8% and heart rate by 45 ± 5%. The beta-3 adrenergic receptor-mediated increase in total peripheral conductance (+146 ± 8%) persisted after combined blockades, i.e., beta and alpha adrenergic, cholinergic, histaminergic, purinergic, prostaglandin and endothelium-derived relaxing factor blockades. Studies that used radioactive microspheres demonstrated a different pattern of regional blood flow distribution with beta-3 adrenergic receptor stimulation compared with ISO- induced beta-1 and beta-2 adrenergic receptor-mediated peripheral vasodilation, i.e., BRL37344 increased blood flow preferentially to the skin (+570 ± 159%) and fat (+685 ± 195%) and the response was not affected by propranolol. Thus, in conscious dogs pretreated with propranolol, beta-3 adrenergic receptor stimulation induced sustained peripheral vasodilation, primarily in the skin and fat. The mechanism appears to be independent of generally recognized mediators of peripheral vasodilation.