The role of metoprolol on cardiac sympathetic signal transduction in a stressed rabbit model

PAN Yu; LIU Ming-ming; GUO Shuai; GU Xingbo; YIN Dechun

doi:10.3969/j.issn.1671-6450.2017.01.006

Abstract：Objective To investigate the effects of metoprolol on β-AR-AC-cAMP pathway and ventricular stability in stressed rabbit model .Methods Thirty male rabbits were randomly divided into control group ( n =10 ) , stressed group ( n =10 ) , stressed plus metoprolol treatment group ( n =10 ) .Complex stimulations of sound and electricity for 24 hours were used to establish acute stressed model .To detect ventricular fibrillation induce rate in each group , we measured the ser-um epinephrine(E), norepinephrine(NE)in the rabbit serum and evaluated the myocardial β-adrenergic receptor (β-AR) density, adenylate cyclase (AC) activity and cyclic adenosine monophosphate (cAMP) levels in ventricular tissues.Results Ventricular fibrillation induce rate in stressed group was significantly higher than control group (χ2 =6.270, P =0.012), the induce rate in treatment group was lower than stressed group (χ2 =9.600, P =0.002),but there was no difference be-tween and treatment group control group (χ2 =0.457, P =0.499).Serum E, NE were higher in stressed group compared to control group ( q =22.49, P <0.01;q =33.64, P <0.01), and were lower in treatment group compared to stressed group ( q =6.45, P <0.01;q =9.76, P <0.01).Ventricular AC activity and cAMP were higher in stressed group compared to control group ( q =34.70, P <0.01;q =11.74, P <0.01), and were lower in treatment group compared to stressed group ( q =21.61, P <0.01;q =4.52, p =0.004).Ventricular β-AR density was significantly higher in stressed group com-pared to control group ( q =8.36, P <0.01), but no significant differences were found between treatment group and stressed group (q =2.21, p =0.129).Equilibrium dissociation constants (KD values) are also appealed no significant difference among these three groups ( F =1.096, P =0.349).Conclusion By inhibiting the β-AR-AC-cAMP signal transduction pathway and inhibiting the sympathetic excitation , decreasing of NE and E release , and improve the stability of the ventricle .