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Background Angiotensin Ⅱ(Ang Ⅱ)acting at angiotensin AT_1 receptor(AT_1R)has well documented effects oncardiovascular structure such as the promotion of cardiovascular hypertrophy and fibrosis,which are believed to beopposed by angiotensin AT_2 receptor(AT_2R)stimulation.The expressions of AT_1R and AT_2R are up-regulated insenescent hearts.The purpose of this study was to investigate the interaction of signal transduction between AT_1R andAT_2R,and to detect whether there is any difference in the interaction in rat hearts of different age.Methods In 3.5-,12-,18- and 24-month-old rats,the heart cell membrane activities of protein kinase C(PKC)andtyrosine kinase were measured when AT_1R and AT_2R were both activated by Ang Ⅱ or just the AT_1R was activated by AngⅡ and PD123319.The activities of cytosolic phospholipase A_2(cPLA_2)and the levels of cGMP were investigated whenAT_1R and AT_2R were both activated by Ang Ⅱ or just the AT_2R was activated by Ang Ⅱ and Iosartan.Results When AT_1R and AT_2R were both activated compared to when the AT_1R was activated,the activities of PKCwere not different in hearts from 3.5- and 12-month-old rats,but decreased significantly in 18- and 24-month-old rats;theactivities of tyrosine kinase were not different in 3.5-month-old rats but decreased significantly in 12-,18- and24-month-old rats.The activities of cPLA_2 were all decreased significantly in rats of different age when AT_1R and AT_2Rwere both activated compared to when the AT_2R was activated.Treatment with Ang Ⅱ alone compared to Ang Ⅱ andIosartan 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-oldrats,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).Conclusions The activation of AT_1R inhibited the signal transduction of AT_2R during the aging variation,and theactivation of AT_2R inhibited the signal transduction of AT_1R in rat heart of different age.
Background Angiotensin Ⅱ (AT_1R) has a documented effect on angiotensin AT_1 receptor (AT_1R) and its promotion of cardiovascular hypertrophy and fibrosis, which are believed to be beposed by angiotensin AT_2 receptor (AT_2R) stimulation.The expressions of AT_1R and The purpose of this study was to investigate the interaction of signal transduction between AT_1R and AT_2R, and to detect whether there is any difference in the interaction in rat hearts of different age. Methods 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_1R and AT_2R were both activated by Ang Ⅱ or just the AT_1R was activated by Ang Ⅱ and PD123319.The activities of cytosolic phospholipase A_2 (cPLA_2) and the levels of cGMP were investigated whenAT_1R and AT_2R were both activated by Ang Ⅱ or just the AT_2R was activated by Ang Ⅱ and Iosartan. Resu lts When AT_1R and AT_2R were both activated compared to when AT_1R was activated, the activities of PKC not different in hearts from 3.5- and 12-month-old rats, but decreased significantly in 18- and 24-month-old rats; theactivities of tyrosine kinase were not different in 3.5-month-old rats but decreased significantly in 12-, 18- and 24-month-old rats. These activities of cPLA 2 were all decreased significantly in rats of different age when AT 1 R and AT 2 Rwere both activated compared to when the AT_2R was activated. Treatment with Ang Ⅱ alone compared to AngII andosartan 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-oldrats, 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) .Conclusions The activation of AT_1R inhibited the signal transduction of AT_2R during the aging variation, and the activation of AT_2 R inhibited the signaltransduction of AT_1R in rat heart of different age.