Relationship between beta-adrenergic receptor numbers and physiological responses during experimental canine myocardial ischemia

In the present study, we evaluated the physiological responsiveness of the increased numbers of beta-adrenergic receptors in ischemic canine myocardium to in vivo stimulation by (-)-isoproterenol and epinephrine. After 1 hour of temporary proximal left anterior descending coronary artery occlusion and during a 15-minute period of reflow, dogs received (1)-isoproterenol intravenously at a rate sufficient to increase their heart rates 20--40 beats/min. Following the infusion of isoproterenol, myocardial tissue was obtained from the LV ischemic and nonischemic regions for measurement of beta-adrenergic receptor numbers, cyclic AMP content, and phosphorylase b to a conversion. beta-Adrenergic receptor numbers were significantly increased in the left ventricular (LV) ischemic tissue. The administration of (-)-isoproterenol was associated with significant increases in cyclic adenosine monophosphate content and phosphorylase b to a conversion in the LV ischemic tissue. Also, the administration of (-)-epinephrine significantly increased the phosphorylase b to a conversion in ischemic tissue over the nonischemic tissue and this conversion was blocked by pretreatment with (+/-)-propranolol. These data suggest that, in this experimental model, the increased numbers of beta-adrenergic receptors in canine LV ischemic tissue are capable of translating physiological responses when they are activated with an appropriate agonist in vivo.