ABSTRACT
[ ABSTRACT] AIM:To investigate the cardiac AMP-activated protein kinase ( AMPK) activity and the effects of AMPK activator on cardiac structure and function in the mice with different β-adrenoceptor (β-AR) stimulation patterns . METHODS:Male BALB/c mice were subcutaneously injected with AMPK activator ( AICAR, 250 mg· kg -1 · d-1 ) or saline, and infused with β-AR agonist isoproterenol (ISO, 5 mg· kg-1· d-1) for 14 d.The cardiac functions were evalu-ated by echocardiography or hemodynamic method , and the hearts were harvested after infusion cessation immediately or 3 d later.Phosphorylated AMPK ( p-AMPK) was measured by Western blot .RESULTS:Sustained ISO infusion increased p-AMPK level.AICAR did not further increase p-AMPK but attenuated ISO-induced increase in heart weight .Sustained ISO infusion increased cardiac systolic function as indicated by left ventricular fractional shortening ( FS) and maximum rate of pressure rise (+dp/dtmax).The cardiac systolic function was not further increased by AICAR .The cardiac diastolic func-tion as indicated by left ventricular end-diastolic pressure (LVEDP) was not different in each group .In contrast, cardiac p-AMPK level was similar between the control mice and the mice with sustained ISO infusion and ceased infusion for 3 d. In this model, AICAR improved the cardiac systolic and diastolic functions , which were impaired by ISO.Moreover, the increased pattern of p-AMPK level was similar with that of heart rate upon ISO stimulation .CONCLUSION: Sustained ISO infusion increases p-AMPK.After ISO infusion cessation for 3 d, p-AMPK is decreased to the basal level .β-AR-in-duced inotropic effects should be avoided to investigate the cardioprotective role of AMPK activation in the β-AR stimulation models.
ABSTRACT
Beta-adrenoceptors (β-AR), members of the G protein-coupled receptors play important roles in the regulation of heart function. A positive inotropic action of catecholamines is mediated through their interaction with β-AR, located on the sarcolemma, while they can also mediate some deleterious effects, such as cardiac arrhythmias or myocardial apoptosis. The well-known β-AR-associated signaling in heart is composed of a coupled mechanism among both β1- and β2-AR and stimulatory G protein (Gs). This coupled mechanism further leads to the activation of adenylyl cyclase and thereby increases in intracellular cAMP level. However, recent studies have emphasized the contribution of constitutive β3-AR coupling to Gi proteins, thereby initiating additional signal transduction pathways, particularly under physiopathological conditions. Diabetic cardiomyopathy, as a distinct entity is recognized due to its diminished responsiveness to β1-AR agonist stimulation in the heart from diabetic rats with no important changes in the responses mediated with β2-AR. Furthermore, an upregulation of β3-AR has been shown in diabetic rat heart with a strong negative inotropic effect on left ventricular function. Experimental data provide evidences that the mechanisms for the negative inotropic effect with β3-AR activation appear to involve a pertussis toxin (PTX)-sensitive G protein and the activation of a nitric oxide synthase pathway. On the other hand, β-blockers demonstrate marked beneficial effects in heart dysfunction with scavenging free radicals and/or acting as an antioxidant with both sex- and dose-dependent manner. However, further investigations are needed to clarify the roles of both altered expression and/or responsiveness of β-AR and the benefits with β-blocker treatment in diabetes. This review discusses the role of β-AR activation, particularly β3-AR in cardiac pathological remodeling under hyperglycemia.
Subject(s)
Animals , Cardiovascular Diseases/immunology , Diabetes Complications/immunology , Gene Expression Regulation/immunology , Humans , Hyperglycemia/immunology , Models, Cardiovascular , Models, Immunological , Myocardium/immunology , Receptors, Adrenergic, beta-3/immunology , Signal Transduction/immunologyABSTRACT
The overactive bladder syndrome (OAB) is a prevalent condition among adults. Currently, the present treatment is mainly conservative therapy. Antimuscarinic drugs are currently the first-line treatment for OAB. However, many patients experienced insufficient therapeutic benefit and/or unpleasant side effects. Recent advances in the understand-ing of the physiopathology of OAB have driven a huge amount of basic and clinical research into novel pharmacological com-pounds.β3-adrenoceptor agonists are an emerging drug class for the treatment of the OAB. This study reviewed the pharma-cological profile ofβ3-adrenoceptor agonists and discussed the efficacy, safety and tolerability.
ABSTRACT
ObjectiveTo investigate the effect of β-adrenoceptor (β-AR) blockers on G protein and heart function changes in rats with acute myocardial infarction (AMI) MethodsWistar rats with AMI induced by left anterior descending coronary branch ligation were randomly divided into compared with sham operation group. Eight weeks after therapy, hemodynamics was assessed by inserting catheters and the level of G protein was detected by Western blot analysis. ResultsCompared with the sham operation group, systolic blood pressure(SBP), diastolic blood pressure (DBP), left ventricular systolic pressure(LVSP) and left ventrieular pressure maximal rate of rise and fall(±dp/dtmax) in AMI group were significantly decreased, while left ventricular end diastolic pressure (LVEDP) and Gs and Gi protein levels were significantly increased (all P<0.05). Compared with AMI group, LVSP and ± dp/dtmax were increased, but LVEDP and Gi protein level were significantly decreased in metoprolol and carvedilol group. LVEDP and Gi protein level were decreased in carvedilol group compared with metoprolol group. ConclusionsCarvedilol can effectively suppress the change of G protein and improve the heart function after AMI, and the effect is better than that of metoprolol. This may be related with its β2-AR blocking effect.