Irbesartan reduces chronic ischemic myocardial injury by up-regulating connexin 43 expression in rats

This study was conducted to investigate the impact and possible mechanisms of irbesartan on the expression of gap junction protein 43 (connexin, Cx43) in rats with myocardial injury. Fifty rats (8-12 week old, weighting 300 ± 50 g) were used as model of chronic myocardial infarction. The rats were divided into sham (thoracotomy only), infracted models without or with irbesartan treatment for two weeks. The survived rats were measured for heart rate (HR), left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LVEDP), the maximal rate of rise of left ventricular pressure (+dP/dtmax) and the maximal rate of decrease of left ventricular pressure (-dP/ dtmax), apoptosis assay using the TUNEL method and Cx43 level using immunofluorescence microscopy, qRT-PCR and Western blot. The levels of cardiac troponin I (cTnI) were also determined. Compared with sham group, infarction group had significantly more apoptotic cells (P < 0.05) and reduced levels of Cx43 at both protein and mRNA levels (P < 0.05). Compared with infarction group, irbesartan reduced the downregulation of Cx43 expression. cTnI contents were 6.37 ± 0.98 ng/ml in sham group, 10.97 ± 1.28 ng/ml in infarction model and 7.65 ± 0.41 ng/ ml in irbesartan group, suggesting that irbesartan has protective effect on myocardial tissue. It is concluded that Irbesartan protects myocardial cells from chronic ischemic injury by increasing Cx43 expression in myocardial cells.