Subtypes of /3-Adrenergic Receptors in Bovine Coronary Arteries

Whether large coronary artery dilation induced by /3-adrenergic stimulation is mediated by /3ior /32adrenergic receptors remains controversial. This problem is particularly difficult to address in vivo due to the concomitant increase in coronary blood flow with /3-adrenergic stimulation, which by itself can dilate large coronary arteries. To reconcile this problem, 5 calves were instrumented with intraaortic and intracoronary (i.e.) catheters, ultrasonic diameter transducers, Doppler flow transducers, and hydraulic occluders on the left circumflex coronary artery. Two to six weeks following surgery, /3-adrenergic agonists were administered i.e. to avoid complicating systemic effects. Isoproterenol (0.0025 fig/kg, a f3t + $2-adrenergic agonist) increased coronary diameter (7.1 ± 0.8% from 5.80 ± 0.58 mm) (p<0.01). Similar increases (p<0.01) in coronary diameter occurred with prenalterol (0.4 Mg/kg> £i-adrenergic agonist) (9.5 ± 1.4%) and pirbuterol (0.25 figfkg, /32-adrenergic agonist) (8.1 ± 1.2%). When coronary blood flow was prevented from rising with the hydraulic constrictor, increases in coronary diameter to all three /3-adrenergic agonists were not attenuated. Large coronary artery dilation with prenalterol and pirbuterol was abolished with fS,and /32adrenergic receptor blockade, respectively, while neither /3,nor /32-adrenergic blockade alone abolished the large coronary artery dilation with isoproterenol. To identify the predominant subtype of /3adrenergic receptor, competitive inhibition curves utilizing I-cyanopindok)l (I-CYP) as the radiolabel versus isoproterenol, epinephrine, and norepinephrine were generated in membrane preparations from calf heart (predominant /3,), calf lung (predominant /32) and calf coronary artery. The coronary artery membrane preparations demonstrated an intermediate pattern. Competition curves with selective /3iand /32-adrenergic receptor agonists and antagonists again demonstrated a pattern for coronary artery intermediate to that of heart and lung, further confirming the presence of both /3adrenergic receptor subtypes in large coronary arteries, with a ratio of fa'-fa of 1.5-2.0:1.0. Thus, large coronary arteries of the calf contain both /S,and /32-adrenergic receptors identified utilizing ligand binding techniques, and stimulation of both receptor subtypes in the intact conscious animal results in large coronary artery dilation, independent of blood-flow-mediated vasodilation. (Circulation Research 1986;59:463-473)