Ferrara Nicola, Abete Pasquale, Corbi Graziamaria, Paolisso Giuseppe, Longobardi Giancarlo, Calabrese Claudio, Cacciatore Francesco, Scarpa Donatella, Iaccarino Guido, Trimarco Bruno, Leosco Dario, Rengo Franco
Department of Health Sciences, University of Molise, Salvatore Maugeri Foundation, IRCCS, Scientific Institute of Telese/Campoli, Via dei Bagni Vecchi, 82037 Telese Terme, Italy.
Am J Hypertens. 2005 Mar;18(3):348-53. doi: 10.1016/j.amjhyper.2004.10.006.
The aim was to investigate the ability of insulin to modulate the response to beta-adrenergic action on myocardial contractility, assessed as percentage changes of developed tension, in isolated rat papillary muscle.
Dose-response curves for isoproterenol, calcium, and forskolin were constructed in an incremental fashion with the presence or absence of insulin at the dose of 50 muU/mL. Dose-response curves for isoproterenol on insulin background were also assessed in the presence and absence of a selective antagonist for beta(2)-adrenoceptor, ICI, at the dose of 5 x 10(-8) mol/L.
Insulin did not modify the dose-response curve to calcium (EC(50): 1.4 +/- 0.4 mmol/Lfor insulin, n = 8 v 1.5 +/- 0.3 mmol/L for control, n = 8; P = not significant), whereas it was able to shift to the left the dose-response curve and reduce significantly the EC(50) of isoproterenol (EC(50): 0.2 +/- 0.2 nmol/L for insulin, n = 13 v 1.1 +/- 0.4 nmol/L for control, n = 12; P < .01). ICI shifted to the right dose-response curve of isoproterenol and increased about 10-fold the EC(50) value of isoproterenol, but insulin was still able to shift to the left dose-response curve of isoproterenol and to reduce significantly the EC(50) of isoproterenol also in the presence of ICI (EC(50): 11.0 +/- 1.5 nmol/L for ICI, n = 7 v 1.9 +/- 0.8 nmol/L for ICI + insulin, n = 7; P < .01). Insulin did not modify the dose-response curve to forskolin.
Our results suggest that the insulin-induced modulation of contractility is calcium independent and insulin leads to a supersensitization on the beta(1)-adrenoceptors without effects on beta-adrenoceptor independent adenylate cyclase-related pathway.
目的是研究胰岛素调节离体大鼠乳头肌对β-肾上腺素能作用于心肌收缩力反应的能力，以舒张张力的百分比变化来评估。
在存在或不存在50 μU/mL胰岛素的情况下，以递增方式构建异丙肾上腺素、钙和福斯高林的剂量-反应曲线。在存在和不存在5×10⁻⁸ mol/L的β₂-肾上腺素能受体选择性拮抗剂ICI的情况下，也评估了胰岛素背景下异丙肾上腺素的剂量-反应曲线。
胰岛素未改变钙的剂量-反应曲线（胰岛素组的半数有效浓度[EC₅₀]：1.4±0.4 mmol/L，n = 8；对照组为1.5±0.3 mmol/L，n = 8；P = 无显著差异），而它能够使异丙肾上腺素的剂量-反应曲线左移并显著降低其EC₅₀（胰岛素组的EC₅₀：0.2±0.2 nmol/L，n = 13；对照组为1.1±0.4 nmol/L，n = 12；P <.01）。ICI使异丙肾上腺素的剂量-反应曲线右移并使异丙肾上腺素的EC₅₀值增加约10倍，但在存在ICI的情况下，胰岛素仍能使异丙肾上腺素的剂量-反应曲线左移并显著降低其EC₅₀（ICI组的EC₅₀：11.0±1.5 nmol/L，n = 7；ICI +胰岛素组为1.9±0.8 nmol/L，n = 7；P <.01）。胰岛素未改变福斯高林的剂量-反应曲线。
我们的结果表明，胰岛素诱导的收缩力调节与钙无关，且胰岛素导致β₁-肾上腺素能受体超敏，而对与β-肾上腺素能受体无关的腺苷酸环化酶相关途径无影响。
