Hunt R A, Ciuffo G M, Saavedra J M, Tucker D C
Department of Psychology, University of Alambama at Birmingham 35294, USA.
J Mol Cell Cardiol. 1995 Nov;27(11):2445-52. doi: 10.1006/jmcc.1995.0232.
Angiotensin II acts as a cardiac growth factor, and causes both inotropic and chronotropic changes within the heart. In the present study, we used an in oculo model system to examine the effects of sympathetic innervation on the density of cardiac angiotensin II receptors. Quantitative autoradiography was used to determine the density of angiotensin II receptors in embryonic rat hearts grafted into either sympathetically innervated or sympathetically denervated eye chambers of adult host rats. The density of specific binding to angiotensin II receptors was nearly three-fold higher in sympathetically non-innervated compared to sympathetically innervated heart grafts (30.8 +/- 4.2 v 11.5 +/- 3.2 fmol/mg protein). Specific binding to angiotensin II receptors in heart grafts was displaced by addition of the AT1 receptor antagonist losartan, but not by addition of the AT2 receptor competitor PD 123177. Thus, only AT1 receptors were present in sympathetically innervated and sympathetically non-innervated embryonic rat hearts grafted in oculo. We conclude that changes in sympathetic innervation caused changes in the density of cardiac angiotensin II receptors in the present study. Our results may have implications for growth and function not only during cardiac development, but also during cardiac disease.
血管紧张素II作为一种心脏生长因子,可引起心脏的变力性和变时性变化。在本研究中,我们使用眼内模型系统来研究交感神经支配对心脏血管紧张素II受体密度的影响。采用定量放射自显影法测定移植到成年宿主大鼠交感神经支配或去交感神经支配眼房内的胚胎大鼠心脏中血管紧张素II受体的密度。与交感神经支配的心脏移植物相比,交感神经未支配的心脏移植物中血管紧张素II受体的特异性结合密度高近三倍(30.8±4.2对11.5±3.2 fmol/mg蛋白)。加入AT1受体拮抗剂氯沙坦可使心脏移植物中血管紧张素II受体的特异性结合发生位移,但加入AT2受体拮抗剂PD 123177则不能。因此,眼内移植的交感神经支配和交感神经未支配的胚胎大鼠心脏中仅存在AT1受体。我们得出结论,在本研究中,交感神经支配的变化导致了心脏血管紧张素II受体密度的变化。我们的结果可能不仅对心脏发育期间,而且对心脏疾病期间的生长和功能都有影响。