Metoprolol and Nebivolol Prevent the Decline of the Redox Status of Low-Molecular-Weight Aminothiols in Blood Plasma of Rats During Acute Cerebral Ischemia.

Abstract

Cerebral ischemia has previously been shown to cause a systemic decrease in levels of the reduced forms of low-molecular-weight aminothiols [cysteine (Cys), homocysteine (Hcy), and glutathione (GSH)] in blood plasma. In this study, we examined the effect of beta-adrenergic receptor (β-AR) antagonists metoprolol (Met) and nebivolol (Neb) on the redox status of these aminothiols during acute cerebral ischemia in rats. We used a model of global cerebral ischemia (bilateral occlusion of common carotid arteries with hypotension lasting for 10 minutes). The antagonists were injected 1 hour before surgery. Total and reduced Cys, Hcy, and GSH levels were measured 40 minutes after the start of reperfusion. Neb (0.4 and 4 mg/kg) and Met (8 and 40 mg/kg) treatment increased the levels of reduced aminothiols and the global methylation index in the hippocampus. The treatments also prevented any decrease in reduced aminothiol levels in blood plasma during ischemia. Although both of these drugs eliminated delayed postischemic hypoperfusion, only Neb reduced neuronal damage in the hippocampus. The results indicate an essential role of β1-AR blockage in the maintenance of redox homeostasis of aminothiols in the plasma and brain during acute cerebral ischemia.