Recovery of cardiac norepinephrine concentration and tyrosine hydroxylase activity by the central alpha(2)-adrenoceptor agonist guanabenz in rats with aortic constriction

Depletion of cardiac norepinephrine has been reported in cardiac hypertroph y. This depletion causes less support for cardiac output in response to sym pathetic nerve activation. The central nervous system is thought to be invo lved in this abnormality. Correction of this abnormality is expected to res tore proper support for the heart. Clipping of the ascending aorta or a sha m operation was performed in 10-week-old rats. At 4 weeks after the operati on, the left ventricular norepinephrine concentration in clipped rats decre ased (p < 0.01). The clipped rats and sham-operated rats were treated with either guanabenz (1 mg/kg) or a vehicle for 4 weeks starting from fifth pos toperative week. The level of left ventricular norepinephrine increased mor e in clipped rats treated with guanabenz (469 +/- 37 ng/g) than in clipped rats treated with a Vehicle (325 +/- 28 ng/g). The norepinephrine concentra tion in the left ventricle recovered significantly after the treatment with guanabenz (p < 0.001). Tyrosine hydroxylase activity in the left ventricle also recovered after treatment with guanabenz (p < 0.01). Modulation of sy mpathetic nerve tone by the alpha(2)-adrenoceptor agonist restored cardiac norepinephrine concentration and tyrosine hydroxylase activity. This could be a new approach to the treatment of heart failure.