Alterations of β-adrenoceptor responsiveness in postischemic myocardium after 72 h of reperfusion

To determine the effect of a completely developed reperfused myocardial infarction model on p-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. beta-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). beta-adrenoceptor density in the ischemic endocardium varied with the degree of collateral blood flow measured (r(2) =0.79, P<0.05); this relation was the opposite of that in the ischemic epicardium (r(2)=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 beta-adrenoceptor activation is dependent upon adenylyl cyclase enzyme activity rather than beta-adrenoceptor density in the ischemic myocardium. However, the density of the beta-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. (C) 2004 Elsevier B.V All rights reserved.