Hilal-Dandan R, Khairallah P A
Department of Heart and Hypertension Research, Cleveland Clinic Foundation, Ohio.
J Mol Cell Cardiol. 1991 Jun;23(6):705-16. doi: 10.1016/0022-2828(91)90980-z.
Impaired inotropic responsiveness to isoproterenol stimulation has been reported in the hypertrophied hearts of spontaneously hypertensive rats and renal hypertensive rats. This study was carried out in order to investigate the possibility that a defect in cyclic AMP production by cardiac myocytes is responsible for the impaired inotropic responsiveness of these hearts. Basal and isoproterenol stimulated cyclic AMP levels were measured in ventricular myocytes isolated from hypertrophied rat hearts. Cyclic AMP accumulation was also measured in the presence of isobutyl-methyl-xanthine, a phosphodiesterase inhibitor, and the results were compared to the appropriate controls. In the spontaneously hypertensive rat, no changes were detected in the basal or isoproterenol stimulated cyclic AMP formation. This suggests that the biochemical alterations leading to a diminished inotropic response in this model of cardiac hypertrophy involve abnormalities in mechanisms other than cyclic AMP production. In the renal hypertensive rat, basal and isoproterenol stimulated cyclic AMP levels were significantly depressed as compared to controls. This suggests that abnormalities in the signal transduction mechanism and formation of cyclic AMP are, at least in part, responsible for the impaired inotropic responsiveness seen in this model. These results confirm that cardiac hypertrophy is a heterogeneous process. Reduced inotropic responsiveness to isoproterenol stimulation in the hypertrophied hearts of the SHR and the RHR, both models of pressure overload hypertrophy, involve different biochemical alterations. Results of this study suggest that the physiologic response of cardiac hypertrophy may not be as important as the underlying cause of hypertrophic stimuli in determining the pathophysiological consequences.
据报道，自发性高血压大鼠和肾性高血压大鼠的肥厚心脏对异丙肾上腺素刺激的变力反应受损。进行这项研究是为了调查心肌细胞中环磷酸腺苷（cAMP）生成缺陷是否是这些心脏变力反应受损的原因。测量了从肥厚大鼠心脏分离的心室肌细胞中的基础cAMP水平和异丙肾上腺素刺激后的cAMP水平。还在磷酸二酯酶抑制剂异丁基甲基黄嘌呤存在的情况下测量了cAMP的积累，并将结果与适当的对照组进行了比较。在自发性高血压大鼠中，基础cAMP形成或异丙肾上腺素刺激后的cAMP形成均未检测到变化。这表明，在这种心脏肥大模型中，导致变力反应减弱的生化改变涉及cAMP生成以外机制的异常。在肾性高血压大鼠中，与对照组相比，基础cAMP水平和异丙肾上腺素刺激后的cAMP水平均显著降低。这表明信号转导机制和cAMP形成的异常至少部分是该模型中所见变力反应受损的原因。这些结果证实心脏肥大是一个异质性过程。在压力超负荷肥大的两种模型——自发性高血压大鼠（SHR）和肾性高血压大鼠（RHR）的肥厚心脏中，对异丙肾上腺素刺激的变力反应降低涉及不同的生化改变。这项研究的结果表明，在决定病理生理后果方面，心脏肥大的生理反应可能不如肥大刺激的潜在原因重要。
