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Objective: To investigate the distribution of beta-adrenoceptors at different sites of heart after myocardial infarction (MI)., Methods: 14 dogs were randomly divided into 2 equal groups: MI group, undergoing ligation of the left anterior descending coronary artery, and control group undergoing sham-operation. Four weeks later metoprolol, a beta 1-adrenergic receptor antagonist, was injected intravenously. Doppler tissue imaging (DTI) was used to evaluate the peak systolic myocardial velocity (Sm) of the regions apical and basal to the infarction region before and after the injection. Then the dogs were killed with their hearts taken out. Reverse-transcriptase polymerase chain reaction was used to examine the mRNA expression of beta 1-receptor and beta 2-receptor in the non-infracted myocardial tissues apical and basal to the infarction region., Results: The Sm values at the regions apical and basal to the infarction region of the MI group were 3.93 +/- 0.47 and 0.81 +/- 0.19 cm/s respectively, both significantly lower than those of the control group (10.84 +/- 1.97 and 5.85 +/- 1.15 cm/s respectively, both P < 0.05). After injection of metoprolol, the Sm values at the regions apical and basal to the infarction region of the MI group were 3.43 +/- 0.37 and 0.73 +/- 0.14 cm/s respectively, not significantly different from those before the injection; however, the corresponding Sm values of the control group were 8.69 +/- 1.14 and 4.33 +/- 0.29 cm/s respectively, both significantly lower than those before the injection (both P < 0.05). The mRNA expression levels of beta 1-receptor decreased in both apical and basal regions in the MI group compared with those in the control group, and the degree of expression decrease at the apical region was significantly greater than that at the basal region. However, there was no significant difference in the expression level of beta 1-receptor mRNA between the apical and basal regions in the control group. There was no significant difference in the mRNA expression of beta 2-receptor in different regions of the heart in both groups., Conclusion: After MI regional variation occurs for the beta 1-receptor mRNA expression, but not to the beta 2-receptor.

Objective: To observe the effects of combined beta(1) adrenergic receptor (AR) antagonist with beta(2)AR agonist therapy on cardiac function and cardiomyocyte apoptosis in heart failure rats., Methods: Heart failure was induced by isoproterenol and rats were randomly divided into metoprolol group (50 mg/kg twice daily/gavage, n = 11), combined treatment group (fenoterol 125 microg/kg and metoprolol 50 mg/kg twice daily/gavage, n = 11) and placebo group (saline, n = 10), another normal 9 male Wistar rats served as control group. After 8 weeks' treatment, cardiac function, apoptosis index (AI), Caspase-3 activity, expression levels of bcl-2 and bax protein, organ weight/body weight and collagen volume fraction (CVF) were evaluated., Results: (1) Left ventricular end diastolic dimension, left ventricular end systolic dimension and E/A ratio were significantly increased and fractional shortening, ejection fraction significantly reduced post isoproterenol (all P < 0.05 vs. control) and these changes were significantly attenuated by metoprolol alone (all P < 0.05 vs. placebo) and further attenuated by the metoprolol and fenoterol combination therapy (all P < 0.05 vs. placebo and metoprolol). (2) Left ventricular weight to body weight ratio, lung weight to body weight ratio and CVF were also significantly reduced in metoprolol and combined treatment group than those in placebo group (all P < 0.01). (3) Compared with placebo group, AI and Caspase-3 activity were significantly lower in metoprolol group (all P < 0.01 vs. placebo) and further reduced in combined treatment group (all P < 0.01 vs. metoprolol). (4) The expression level of bax protein was significantly lower in metoprolol group while bcl-2/bax significantly higher than those in placebo group. These changes were more significant in combined treatment group (all P < 0.01 vs. metoprolol)., Conclusions: beta(1)AR antagonist in combination with beta(2)AR agonist further improved the cardiac function and prevented cardiac remodeling compared with using beta(1)AR antagonist alone in heart failure rats. Downregulated bax and upregulated bcl-2/bax expressions might contribute to the observed beneficial therapy effects by reducing cardiomyocyte apoptosis in these animals.

Aim: To study the role of beta-adrenoceptors (beta-AR) and their subtypes in the control of kindling models in rats., Methods: Electrical amygdala kindling, pentylenetetrazol (PTZ) kindling models in rats and maximal electroshock (MES) in mice were used to observe the effects of beta-AR agonists and antagonists., Results: The beta-AR antagonist propranolol 15 mg.kg-1 i.p. delayed the development of amygdala kindling; while propranolol 1-20 mg.kg-1 i.p. and beta-AR antagonist metoprolol 25-400 mg.kg-1 ig significantly increased the afterdischarge threshold and reduced the seizure severity in both kindling models (P < 0.01). beta 1-AR agonist dobutamine completely reversed the inhibitory effect of propranolol, while the beta 2-AR agonist terbutaline showed no effect on propranolol. Metoprolol 200 and 800 mg.kg-1 ig significantly inhibited MES in mice (P < 0.01)., Conclusion: Central beta 1-AR is involved in the inhibitory effects on amygdala kindling and PTZ kindling models in rats.