Guanabenz significantly increased left ventricular norepinephrine concentration in rats with aortic constriction compared to vehicle (469 vs 325 ng/g; p<0.001).
Does guanabenz restore cardiac norepinephrine concentration and tyrosine hydroxylase activity in rats with aortic constriction?
Central alpha2-adrenoceptor agonism with guanabenz restores cardiac norepinephrine levels and tyrosine hydroxylase activity in a rat model of cardiac hypertrophy, suggesting a potential novel approach for heart failure treatment.
Absolute Event Rate: 469% vs 325%
p-value: p=<0.001
Depletion of cardiac norepinephrine has been reported in cardiac hypertrophy. This depletion causes less support for cardiac output in response to sympathetic nerve activation. The central nervous system is thought to be involved in this abnormality. Correction of this abnormality is expected to restore proper support for the heart. Clipping of the ascending aorta or a sham operation was performed in 10-week-old rats. At 4 weeks after the operation, the left ventricular norepinephrine concentration in clipped rats decreased (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 postoperative week. The level of left ventricular norepinephrine increased more in clipped rats treated with guanabenz (469+/-37 ng/g) than in clipped rats treated with a vehicle (325+/-28 ng/g). The norepinephrine concentration 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 sympathetic nerve tone by the alpha2-adrenoceptor agonist restored cardiac norepinephrine concentration and tyrosine hydroxylase activity. This could be a new approach to the treatment of heart failure.
Takechi et al. (1999) studied Aortic constriction / Cardiac hypertrophy. Guanabenz vs. Vehicle was evaluated on Left ventricular norepinephrine concentration (p=<0.001). Guanabenz significantly increased left ventricular norepinephrine concentration in rats with aortic constriction compared to vehicle (469 vs 325 ng/g; p<0.001).