Effect of pharmaceutical intervention on AT1R, AT2R, ERK and JNK activity in chronic hibernating myocardium in rabbits

Objective To investigate in chronic hibernating myocardium in rabbits and the influence and significance of captopril, betaloc, valsartan in angiotensin II subtype 1 receptor(AT 1 R), angiotensin II subtype 2 receptor(AT 2 R), extracellular signal regulated kinase 1/2 (ERK1/2), c-Jun N-terminal kinase(JNK). Methods The model of chronic hibernating myocardium(CHM) was established. The changes of AT 1 R, AT 2 R, ERK1/2, JNK in different groups were assessed by western blotting and immunohistochemistry. Results The amount of AT 1 R decreased while AT 2 R increased in the CON group compared with in sham group, and both AT 1 R and AT 2 R decreased in drug groups compared with the CON group. The content of ERK had no change in each group, while that of “expression” p-ERK increased in CON group compared with in sham group, and was lower in drug intervention groups than in CON and sham groups. The contents of JNK and p-JNK decreased in CON and drug intervention groups compared with in sham group. The protein levels of JNK, p-JNK in drug intervention groups were lower than in the CON group. Three drugs can inhibit interstitial fibrosis and reduce apoptotic cells. The expression levels in the groups(with different doses) had statistical difference as well as between groups of captopril and other drugs; however the results between betaloc and valsartan had no significant difference. Conclusion AT 1 R, AT 2 R may be the upper stream receptor of ERK and JNK and may participate in generation and evolution of CHM. Captopril, valsartan and betaloc may preserve CHM by inhibiting AT 1 R, AT 2 R and JNK activity.