beta-adrenoceptor density in chronic infarcted myocardium: a subtype specific decrease of beta(1)-adrenoceptor density

beta-adrenoceptor density is altered in different cardiac diseases. In hear t failure beta-adrenoceptor density is down regulated but in acute myocardi al ischemia beta-adrenoceptor density is up regulated. In hearts with myoca rdial infarction total beta-adrenoceptor density is decreased shortly after myocardial infarction. Aims and methods: To investigate whether total beta -adrenoceptor number is altered in the chronic phase after myocardial infar ction, and to identify the specificity of alteration, we studied male Wista r rats (n=18) which underwent a ligation of the left coronary artery or a s ham operation. Twelve weeks after coronary ligation, rats were sacrificed a nd hearts were excised, perfused to obtain blood-free myocardium and frozen in liquid nitrogen. Infarcted myocardium was identified visually and separ ated from non-infarcted myocardium. Total beta-adrenoceptor number was calc ulated in fmol (-)-[I-125]iodocyanopindolol specifically bound/mg protein a nd the relative amount of beta(1)- and beta(2)-adrenoceptor density was mea sured by inhibition of (-)-[I-125] iodocyanopindolol binding with CGP 20712 A. Results: Total beta-adrenoceptor number in infarcted myocardium was sig nificantly decreased (25.7 +/- 1.4 vs. 24.9 +/- 2.2 vs. 20.1 +/- 3.2 fmol/m g protein (P=0.03) resp. Sham vs. Non-infarcted vs. Infarcted myocardium), due to a decrease of only beta(1)-adrenoceptor density (14.7 +/- 0.61 vs. 1 2.7 +/- 1.09 vs. 4.84 +/- 0.96 fmol/mg protein (P=0.004) resp.), whereas th e beta(2)-adrenoceptor density and the dissociation constant (K-d) were not significantly decreased. Conclusion: In the infarcted myocardium total bet a-adrenocepter density is decreased due to a decreased beta(1)-adrenoceptor density at 12 weeks after myocardial infarction. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.