AT2 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 angiotensin II receptor subtypes 1 and 2 in total interstitial cell and endothelial cell DNA synthesis and cardiac function after myocardial infarction (MI) in the rat. Rats with a MI were treated with either AT1 receptor antagonist GR138950C (2 mg/kg/day) or the AT2 receptor antagonist PD123319 (3 mg/kg/day). Total interstitial cell (that is endothelial cells and fibroblast-like cells) DNA synthesis in the interventricular septum was significantly increased 2 weeks after MI. 33+/-3% of DNA synthesizing cells were identified as endothelial cells. PD123319, but not GR138950C significantly reduced total interstitial DNA synthesis. Both agents did not alter the fraction of DNA synthesizing endothelial cells. The effects on cardiac function were studied in parallel groups. MI reduced both cardiac output and stroke volume at 3 weeks after MI PD123319 reduced CO, whereas GR138950C did not affect cardiac function. Thus, the data show that AT2 receptor blockade, but not AT1 receptor blockade early after rat myocardial infarction inhibits interstitial DNA synthesis and decreases cardiac function.
Kuizinga
M C
MC
Department of Pathology, Cardiovascular Research Institute Maastricht, Universiteit Maastricht, The Netherlands.
Smits
J F
JF
Arends
J W
JW
Daemen MJAP
D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001572:Benzofurans / Q000494:pharmacology; D002302:Cardiac Output / Q000187:drug effects; D002455:Cell Division; D004247:DNA / Q000096:biosynthesis*; D004727:Endothelium / Q000378:metabolism / Q000473:pathology; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D013318:Stroke Volume / Q000187:drug effects
D057911:Angiotensin Receptor Antagonists; D001572:Benzofurans; D007093:Imidazoles; D011725:Pyridines; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; C073402:PD 123319; D004247:DNA; C089586:saprisartan potassium