Enzyme-Specific Desensitization of Adenylyl Cyclase in Hypertrophied Heart in Monocrotaline-Treated Rats

Abstract

Monocrotaline (MCT) is a toxic pyrrolidine alkalpid isolated from the stem, foliage and seeds of Crotalaria spectabilis. Administration of MCT to rats results in pulmonary arterial hypertension, leading to a severe right ventricular hypertrophy and eventually to failure [1]. As reported in patients with heart failure caused by primary pulmonary hypertension, a chamber-specific decrease in the myocardial β-adrenoceptors was shown mostly in the failing right ventricle, while the β-adrenoceptor density in the left ventricle remained normal [2]. This phenomenon is explained as the down-regulation of the β-adrenoceptor due to an increased sympathetic nerve activity in a state of congestive heart failure. The goal of the present investigation was to determine whether the mechanism of the desensitiza¬tion was mostly due to the downregulation of β-adrenoceptor or adenylyl cyclase activation in an experimental model of right ventricular failure. Although the phenomenon of desensitization, homologous or heterologous, has been recognized at the in vitro cultured cells, few studies have examined this phenomenon in the in vivo model of heart failure.