Bouanani N, Corsin A, Gilson N, Crozatier B
I.N.S.E.R.M. U2, Hôpital Léon Bernard, Limeil-Brévannes, France.
J Mol Cell Cardiol. 1991 May;23(5):573-81. doi: 10.1016/0022-2828(91)90049-r.
Beta-adrenoceptor density and affinity, studied by H3-CGP 12177 binding, and adenylate cyclase activity were measured in 12 left ventricles of rabbits with heart failure and compared to 13 left ventricles of control (C) rabbits. Heart failure (HF) was induced by a double volume (aortic insufficiency) plus pressure (aortic stenosis 14 days later) overload. Left ventricular mass was increased in HF by 67% above C. Saturation curves with CGP 12177 showed a 36% decrease in beta-adrenoceptor density (C = 61.5 +/- 5.4 fmol/mg prot., P less than 0.05) but competition curves with isoproterenol were not different in HF and C. Basal and Gpp(NH)p stimulated adenylate cyclase activity were decreased by 36% and 22% respectively in rabbits with heart failure as compared with control animals and cAMP production was significantly smaller in failing left ventricles than in control left ventricles both after NaF stimulation (C: 161.3 +/- 24.9 pmols/mg/min; HF: 98.8 +/- 7.0 pmols/mg/min; P less than 0.05) and even more after forskolin stimulation (C: 159.1 +/- 23.9 and HF: 60.8 +/- 7.3 pmols/mg/min; P less than 0.01). Although isoproterenol stimulated ACA was smaller in HF than in C, EC50 was similar in both groups (1.6 x 10(-7) M). We conclude that in the early stage of heart failure in the rabbit, although adrenoceptor density is decreased, there are no changes of affinity of beta-adrenoceptors for isoproterenol and the major alteration of cAMP production appears to lie down-stream the receptor level with a markedly impaired stimulation of adenylate cyclase activity by forskolin.
采用H3-CGP 12177结合法研究β-肾上腺素能受体密度和亲和力，并测定12只心力衰竭家兔左心室的腺苷酸环化酶活性，与13只对照（C）家兔的左心室进行比较。通过双倍容量（主动脉瓣关闭不全）加压力（14天后主动脉瓣狭窄）超负荷诱导心力衰竭（HF）。HF组左心室质量比C组增加67%。CGP 12177的饱和曲线显示β-肾上腺素能受体密度降低36%（C = 61.5 +/- 5.4 fmol/mg蛋白，P < 0.05），但HF组和C组与异丙肾上腺素的竞争曲线无差异。与对照动物相比，心力衰竭家兔的基础腺苷酸环化酶活性和Gpp(NH)p刺激的腺苷酸环化酶活性分别降低36%和22%，在NaF刺激后，衰竭左心室的cAMP生成明显低于对照左心室（C组：161.3 +/- 24.9 pmols/mg/min；HF组：98.8 +/- 7.0 pmols/mg/min；P < 0.05），在福斯可林刺激后差异更显著（C组：159.1 +/- 23.9，HF组：60.8 +/- 7.3 pmols/mg/min；P < 0.01）。尽管HF组中异丙肾上腺素刺激的腺苷酸环化酶活性低于C组，但两组的半数有效浓度（EC50）相似（1.6 x 10(-7) M）。我们得出结论，在兔心力衰竭的早期，尽管肾上腺素能受体密度降低，但β-肾上腺素能受体对异丙肾上腺素的亲和力没有变化，cAMP生成的主要改变似乎位于受体水平下游，福斯可林对腺苷酸环化酶活性的刺激明显受损。
