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Journal of Cardiovascular Pharmacology and Therapeutics
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Prevention of Vascular Apoptosis in Myocardial Infarction by Losartan

Sushil K. Sharma

Donald Chapman

Rana Temsah

Thomas Netticadan

David P. Brasil

Naranjan S. Dhalla

Background: Previous studies have demonstrated the occurrence of apoptosis in cardiomyo cytes in different types of cardiovascular diseases. This report provides the first evidence for the presence of vascular apoptosis in myocardial infarction induced in rats by occluding the coronary artery for 7 weeks.

Methods and Results: Apoptosis was characterized by DNA fragmentation, upregulation of caspase-3, downregulation of poly (ADP-ribose) polymerase (PARP), increased c-fos mRNA expression and caspase-3/PARP ratio in aortic vascular smooth muscle cells. The results show apoptotic changes in 10-25% of the aortic vascular cells after myocardial in farction ; these alterations were prevented after treating the 3-week operated animals with an angiotensin II receptor antagonist, losartan (25 mg/kg/day; intraperitoneal) for 4 weeks. Cultured rat aortic smooth muscle cells exposed to 10 nmol/L angiotensin II for 48 hours also exhibited apoptotic changes, which were inhibited by 10 nmol/L losartan.

Conclusions: These results suggest that vascular apoptosis occurs in myocardial infarction, and this may be due to an increase in the circulating levels of angiotensin II.

Key Words: vascular smooth muscle • apoptosis • myocardial infarction • angiotensin II • losartan.

Journal of Cardiovascular Pharmacology and Therapeutics, Vol. 4, No. 2, 77-84 (1999)
DOI: 10.1177/107424849900400202
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