Bai Hua, Wu Li-ling, Xing Dong-qi, Liu Jie, Zhao Ya-li
Department of Cardiology, Peking Union Medical College Hospital, Beijing 100730, China.
Chin Med J (Engl). 2004 Jan;117(1):88-93.
The role of the G alpha q/11-mediated signal transduction pathway in angiotensin II (AngII) induced cardiac hypertrophy remains unclear. This study was to investigate the role of the G alpha q/11 signal transduction pathway in the development of cardiac hypertrophy in 2K1C hypertensive rats and in cultured neonatal rat ventricular myocytes (NRVMs) and to elucidate the effects of the pathway on AngII induced cardiac hypertrophy.
Renal hypertension was induced in 2K1C hypertensive rats by placing a silver clip around the left renal artery. At 8 weeks after operation, the systolic blood pressure, the ratio of left ventricular weight to body weight (LV/BW), and the concentration of AngII in the heart were measured. The protein levels of G alpha q/11 and extracellular signal-regulated kinase 1/2 (ERK1/2) were assayed by Western blot analysis, and the activity of phospholipase C (PLC) in the myocardium was detected using [(3)H]-PIP2 as a substrate. Changes in [(3)H]-leucine incorporation and in the protein levels of the signal molecules G alpha q/11, PLC beta 3, and ERK1/2 were measured after NRVMs were stimulated with 10(-7) mol/L AngII.
The protein levels of G alpha q/11 and ERK1/2 in the hearts of 2K1C rats increased by 35.8% and 31.9%, respectively, compared with the sham group. The PLC activity in the 2K1C group was also significantly increased (P < 0.05). The levels of G alpha q/11, PLC beta 3, and ERK1/2 increased significantly after NRVMs were stimulated by AngII. The upregulation of G alpha q/11, PLC beta 3 and ERK1/2 in NRVMs occurred prior to [(3)H]-leucine incorporation increases, and could be inhibited with losartan.
AngII can initiate cardiac hypertrophy and upregulate signal molecules in the G alpha q/11-mediated signal transduction pathway, such as G alpha q/11, PLC beta 3 and ERK1/2, at both tissue and cellular levels.
Gαq/11介导的信号转导通路在血管紧张素II（AngII）诱导的心肌肥大中的作用尚不清楚。本研究旨在探讨Gαq/11信号转导通路在2K1C高血压大鼠和培养的新生大鼠心室肌细胞（NRVMs）心肌肥大发生发展中的作用，并阐明该通路对AngII诱导的心肌肥大的影响。
通过在左肾动脉周围放置银夹诱导2K1C高血压大鼠发生肾性高血压。术后8周，测量收缩压、左心室重量与体重之比（LV/BW）以及心脏中AngII的浓度。采用蛋白质印迹分析检测Gαq/11和细胞外信号调节激酶1/2（ERK1/2）的蛋白水平，以[(3)H]-磷脂酰肌醇-4,5-二磷酸（PIP2）为底物检测心肌中磷脂酶C（PLC）的活性。用10(-7)mol/L AngII刺激NRVMs后，测量[(3)H]-亮氨酸掺入量以及信号分子Gαq/11、PLCβ3和ERK1/2的蛋白水平变化。
与假手术组相比，2K1C大鼠心脏中Gαq/11和ERK1/2的蛋白水平分别升高了35.8%和31.9%。2K1C组的PLC活性也显著增加（P<0.05）。AngII刺激NRVMs后，Gαq/11、PLCβ3和ERK1/2的水平显著升高。NRVMs中Gαq/11、PLCβ3和ERK1/2的上调发生在[(3)H]-亮氨酸掺入量增加之前，并且可被氯沙坦抑制。
AngII可在组织和细胞水平引发心肌肥大，并上调Gαq/11介导的信号转导通路中的信号分子，如Gαq/11、PLCβ3和ERK1/2。
