Sethi R, Dhalla K S, Beamish R E, Dhalla N S
Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
Am J Physiol. 1997 Feb;272(2 Pt 2):H884-93. doi: 10.1152/ajpheart.1997.272.2.H884.
The status of beta-adrenergic receptors and adenylyl cyclase in crude membranes from both left and right ventricles was examined when the left coronary artery in rats was occluded for 4, 8, and 16 wk. The adenylyl cyclase activity in the presence of isoproterenol was decreased in the uninfarcted (viable) left ventricle and increased in the right ventricle subsequent to myocardial infarction. The density of beta1-adrenergic receptors, unlike beta2-receptors, was reduced in the left ventricle, whereas no change in the characteristics of beta1- and beta2-adrenergic receptors was seen in the right ventricle. The catalytic activity of adenylyl cyclase was depressed in the viable left ventricle but was unchanged in the right ventricle. In comparison to sham controls, the basal, as well as NaF-, forskolin-, and 5'-guanylyl imidodiphosphate [Gpp(NH)p]-stimulated adenylyl cyclase activities were decreased in the left ventricle and increased in the right ventricle of the experimental animals. Opposite alterations in the adenylyl cyclase activities in left and right ventricles from infarcted animals were also seen when two types of purified sarcolemmal preparations were employed. These changes in adenylyl cyclase activities in the left and right ventricles were dependent on the degree of heart failure. Furthermore, adenosine 3',5'-cyclic monophosphate contents were higher in the right ventricle and lower in the left ventricle from infarcted animals injected with saline, isoproterenol, or forskolin in comparison to the controls. The results suggest differential changes in the viable left and right ventricles with respect to adenylyl cyclase activities during the development of congestive heart failure due to myocardial infarction.
当大鼠左冠状动脉闭塞4周、8周和16周时,检测左、右心室粗制膜中β-肾上腺素能受体和腺苷酸环化酶的状态。心肌梗死后,未梗死(存活)的左心室中异丙肾上腺素存在时的腺苷酸环化酶活性降低,而右心室中该活性升高。与β2-受体不同,左心室中β1-肾上腺素能受体的密度降低,而右心室中β1-和β2-肾上腺素能受体的特性未见变化。存活的左心室中腺苷酸环化酶的催化活性降低,但右心室中该活性未改变。与假手术对照组相比,实验动物左心室中基础的以及氟化钠、福斯可林和5'-鸟苷酰亚胺二磷酸[Gpp(NH)p]刺激的腺苷酸环化酶活性降低,右心室中该活性升高。当使用两种纯化的肌膜制剂时,梗死动物左、右心室中腺苷酸环化酶活性也出现相反的变化。左、右心室中腺苷酸环化酶活性的这些变化取决于心力衰竭的程度。此外,与对照组相比,注射生理盐水、异丙肾上腺素或福斯可林的梗死动物右心室中3',5'-环磷酸腺苷含量较高,左心室中该含量较低。结果表明,在心肌梗死所致充血性心力衰竭发展过程中,存活的左、右心室在腺苷酸环化酶活性方面存在差异变化。