Interaction of signal transduction between angiotensin AT1 and AT2 receptor subtypes in rat senescent heart

BACKGROUND: 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. 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(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. RESULTS: 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). CONCLUSIONS: 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.