The role of β3 adrenergic receptor-mediated protection in in-vivo myocardial ischemia/reperfusion injury model

Beta-3 adrenergic receptors (β3-AR) are negative inotropic response to the classical positive inotropic effects of β1 and β2-ARs in the heart muscle. β3-AR promotes nitric oxide production by activating endothelial nitric oxide synthetase (eNOS) and, causes vasodilatation. β3-ARs have been shown to have protective effects on the cardiovascular system, which is critical in heart diseases such as heart failure, myocardial infarction (MI). However, there are not enough studies that demonstrate the role, functions and sub-pathways of β3-AR in the MI. In this study, we aimed to investigate β3-AR preservation and possible sub-pathways in experimental myocardial ischemia/reperfusion (I/R) injury. For this purpose, we investigated the effect of I/R-induced necrosis area by giving pre-ischemia β3-AR selective agonist BRL37344. In addition, AMPK in autophagy with energy metabolism, SIRT1 which reduces oxidative stress and inhibits apoptosis, mTOR and p70SK6 levels which play role in cell stress reactions were examined. Single dose BRL 37344 (5mcg/kg) was given immediately prior to reperfusion of 120 min ischemia for 30 min. 10 days i.p BRL37344 (5 mcg/kg /day) treated group 11th day I/R was performed. The infarct area was determined by triphenyltetrazolium chloride (TTC) and calculated by ImageJ program. AMPK, SIRT1, mTOR and p70SK6 levels were measured by Western Blot method. The necrosis area was significantly lower in the single-dose group BRL37344 (32,21 ± 1,57) than in the control I/R group (44,84 ± 1,47). AMPK and SIRT1 levels decreased significantly with I/R, but increased significantly in single-dose and 10-day treatment groups. mTOR and p70S6K levels increased significantly with I/R. mTOR and p70S6K levels approached control in BRL37344 treated group, significantly decreased. The β3-AR stimulation may be important for the protection against I/R damage. These findings have shown that AMPK, SIRT1, mTOR and p70S6K levels may have a role in β3-AR protection.