Abstract

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 micrograms/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 micrograms/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.(ABSTRACT TRUNCATED AT 250 WORDS)