Sodium valproate reverses aortic hypercontractility in acute myocardial infarction in rabbits.

Sympathetic nervous system (SNS), endothelin 1 (ET-1) and angiotensin II (Ang II) are involved in the pathophysiology of acute myocardial infarction (AMI). Valproic acid (VPA) is under study for the treatment against AMI due to its beneficial cardiac effects. However, the vascular effects of VPA on the activation of the SNS, ET-1 and Ang II after AMI are not fully studied. In our study, we used aorta from New Zealand White rabbits without AMI, with AMI and AMI treated with VPA (500 mg/kg/day). AMI was induced by occluding the left circumflex coronary artery for 1 h, followed by reperfusion. After 5 weeks, we studied the ex vivo vascular reactivity in organ bath and measured protein expression by Western blot. Our findings indicated that AMI increased vasoconstriction to exogenous and endogenous NE and ET-1, which was reversed by VPA eliciting upregulation of α-adrenergic and ETB receptors and downregulating ETA receptors. Although no changes in the vascular response to Ang II were observed in AMI or VPA-treated rabbits, an increase in Ang II type 2 receptor expression was found in VPA-treated rabbits. We conclude that VPA could be considered a vascular protector by modulating SNS, ET-1 and Ang II in the aorta, which together with its cardioprotective effect would make it a promising candidate for the treatment of AMI.