Desensitization of cardiac β-adrenoceptor signaling with heart failure produced by myocardial infarction in the rat. Evidence for the role of Gi but not Gs or phosphorylating proteins

Abstract

This study examined mechanisms of β-adrenergic (AR) desensitization in a myocardial infarction (MI) model of heart failure in the rat. Isotropic responses to isoproterenol (non-selective β-AR agonist) and RO 363 (selective β1-AR agonist), in left atria and left papillary muscle, were reduced by up to 65%, while chronotropic responses in right atria were unaffected. β1- and β2-AR density did not change after MI, suggesting that changes in β-AR responsiveness are due to changes occurring downstream of the receptor. Inotropic and chronotropic responses to forskolin were not altered in right and left atria and left papillary muscle after MI, suggesting changes at the level of the G-proteins. Per..