Shi Shu-tian, Li Yan-fang
Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China.
Chin Med J (Engl). 2007 Oct 20;120(20):1820-4.
Angiotensin II (Ang II) acting at angiotensin AT(1) receptor (AT(1)R) has well documented effects on cardiovascular structure such as the promotion of cardiovascular hypertrophy and fibrosis, which are believed to be opposed by angiotensin AT(2) receptor (AT(2)R) stimulation. The expressions of AT(1)R and AT(2)R are up-regulated in senescent hearts. The purpose of this study was to investigate the interaction of signal transduction between AT(1)R and AT(2)R, and to detect whether there is any difference in the interaction in rat hearts of different age.
In 3.5-, 12-, 18- and 24-month-old rats, the heart cell membrane activities of protein kinase C (PKC) and tyrosine kinase were measured when AT(1)R and AT(2)R were both activated by Ang II or just the AT(1)R was activated by Ang II and PD123319. The activities of cytosolic phospholipase A(2) (cPLA(2)) and the levels of cGMP were investigated when AT(1)R and AT(2)R were both activated by Ang II or just the AT(2)R was activated by Ang II and losartan.
When AT(1)R and AT(2)R were both activated compared to when the AT(1)R was activated, the activities of PKC were not different in hearts from 3.5- and 12-month-old rats, but decreased significantly in 18- and 24-month-old rats; the activities of tyrosine kinase were not different in 3.5-month-old rats but decreased significantly in 12-, 18- and 24-month-old rats. The activities of cPLA(2) were all decreased significantly in rats of different age when AT(1)R and AT(2)R were both activated compared to when the AT(2)R was activated. Treatment with Ang II alone compared to Ang II and losartan decreased the levels of cGMP (fmol/mg) in rats of different age (102.7 +/- 12.7 versus 86.0 +/- 8.0 in 3.5-month-old rats, P < 0.05; 81.0 +/- 9.4 versus 70.0 +/- 6.3 in 12-month-old rats, P < 0.05; 69.8 +/- 5.6 versus 54.2 +/- 5.3 in 18-month-old rats, P < 0.01; 57.7 +/- 8.0 versus 39.0 +/- 3.0 in 24-month-old rats, P < 0.01).
The activation of AT(1)R inhibited the signal transduction of AT(2)R during the aging variation, and the activation of AT(2)R inhibited the signal transduction of AT(1)R in rat heart of different age.
作用于血管紧张素AT1受体（AT1R）的血管紧张素II（Ang II）对心血管结构具有诸多已被充分证实的影响，如促进心血管肥大和纤维化，而血管紧张素AT2受体（AT2R）的刺激被认为可对抗这些影响。AT1R和AT2R的表达在衰老心脏中上调。本研究的目的是探讨AT1R和AT2R之间信号转导的相互作用，并检测不同年龄大鼠心脏中这种相互作用是否存在差异。
在3.5、12、18和24月龄大鼠中，当AT1R和AT2R均被Ang II激活或仅AT1R被Ang II和PD123319激活时，测量蛋白激酶C（PKC）和酪氨酸激酶的心肌细胞膜活性。当AT1R和AT2R均被Ang II激活或仅AT2R被Ang II和氯沙坦激活时，研究胞质磷脂酶A2（cPLA2）的活性和cGMP的水平。
与仅激活AT1R相比，当AT1R和AT2R均被激活时，3.5和12月龄大鼠心脏中PKC的活性无差异，但在18和24月龄大鼠中显著降低；3.5月龄大鼠中酪氨酸激酶的活性无差异，但在12、18和24月龄大鼠中显著降低。与仅激活AT2R相比，当AT1R和AT2R均被激活时，不同年龄大鼠中cPLA2的活性均显著降低。与Ang II和氯沙坦相比，单独用Ang II处理降低了不同年龄大鼠中cGMP的水平（3.5月龄大鼠中为102.7±12.7对vs 86.0±8.0，P<0.05；1个月龄大鼠中为81.0±9.4对vs 70.0±6.3，P<0.05；18月龄大鼠中为69.8±5.6对vs 54.2±5.3，P<0.01；24月龄大鼠中为57.7±8.0对vs 39.0±3.0，P<0.01）。
在衰老过程中，AT1R的激活抑制了AT2R的信号转导，且在不同年龄大鼠心脏中，AT2R的激活抑制了AT1R的信号转导。
