AT(2) RECEPTOR BLOCKADE REDUCES CARDIAC INTERSTITIAL CELL-DNA SYNTHESIS AND CARDIAC-FUNCTION AFTER RAT MYOCARDIAL-INFARCTION

The objective of the study was to investigate the involvement of angio tensin II receptor subtypes 1 and 2 in total interstitial cell and end othelial cell DNA synthesis and cardiac function after myocardial infa rction (MT) in the rat. Rats with a MI were treated with either AT(1) receptor antagonist GR138950C (2 mg/kg/day) or the AT(2) receptor anta gonist PD123319 (3 mg/kg/day). Total interstitial cell (that is endoth elial cells and fibroblast-like cells) DNA synthesis in the interventr icular septum was significantly increased 2 weeks after MI. 33 +/- 3% of DNA synthesizing cells were identified as endothelial cells. PD1233 19, but not GR138950C significantly reduced total interstitial DNA syn thesis, Both agents did not alter the fraction of DNA synthesizing end othelial cells. The effects on cardiac function were studied in parall el groups. MI reduced both cardiac output and stroke volume at 3 weeks after MI PD123319 reduced CO, whereas GR138950C did not affect cardia c function. Thus, the data show that AT(2) receptor blockade, but not AT(1) receptor blockade early after rat myocardial infarction inhibits interstitial DNA synthesis and decreases cardiac function. (C) 1998 A cademic Press Limited.