To determine the effect of a completely developed reperfused myocardial infarction model on β-adrenoceptor responsiveness, we induced a 90-min regional ischemia followed by 72 h of reperfusion in dog hearts. Regional myocardial blood flow was determined after 60 min of ischemia using radioactive microspheres. β-adrenoceptor density was reduced in the ischemic endocardium (95±16 fmol/mg) and epicardium (160±13 fmol/mg) compared to the nonischemic region (304±21 fmol/mg). β-adrenoceptor density in the ischemic endocardium varied with the degree of collateral blood flow measured (r2=0.79, P<0.05); this relation was the opposite of that in the ischemic epicardium (r2=0.77, P<0.05). Higher levels of tissue catecholamines and G protein-coupled receptor kinase 2 (GRK2) were observed in the ischemic epicardium as compared to nonischemic tissue. Forskolin-induced adenylyl cyclase activities were depressed in both ischemic regions as compared to nonischemic region, correlating with a reduction in regional myocardial blood flow. Using forskolin stimulation as covariate, no difference in isoproterenol-induced adenylyl cyclase activity was identified in the different regions.
It is concluded that cAMP production induced by β-adrenoceptor activation is dependent upon adenylyl cyclase enzyme activity rather than β-adrenoceptor density in the ischemic myocardium. However, the density of the β-adrenoceptor in the viable ischemic regions can be modified by the presence of GRK2 and tissue catecholamines, an index of regional sympathetic efferent postganglionic nerve terminal activity.