Limits...
β2 adrenergic receptor activation governs cardiac repolarization and arrhythmogenesis in a guinea pig model of heart failure.

Wang Y, Yuan J, Qian Z, Zhang X, Chen Y, Hou X, Zou J - Sci Rep (2015)

Bottom Line: These effects could be prevented by the selective β2-AR antagonist, ICI118551.Salbutamol prolonged APD90 and reduced Ikr in guinea pig HF myocytes.However, the antagonists of Gi protein (PTX) and PDE III (amrinone) showed opposite effects.

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.

ABSTRACT
β2-AR activation increases the risk of sudden cardiac death (SCD) in heart failure (HF) patients. Non-selective β-AR blockers have greater benefits on survival than selective β1-AR blockers in chronic HF patients, indicating that β2-AR activation contributes to SCD in HF. This study investigated the role of β2-AR activation on repolarization and ventricular arrhythmia (VA) in the experimental HF model. The guinea pig HF was induced by descending aortic banding. The effective refractoriness period (ERP), corrected QT (QTc) and the incidence of VA were examined using Langendorff and programmed electrical stimulation. Ikr and APD were recorded by the whole cell patch clamp. Selective β2-AR agonist salbutamol significantly increased the incidence of VA, prolonged QTc and shortened ERP. These effects could be prevented by the selective β2-AR antagonist, ICI118551. Salbutamol prolonged APD90 and reduced Ikr in guinea pig HF myocytes. The antagonists of cAMP (Rp-cAMP) and PKA (KT5720) attenuated Ikr inhibition and APD prolongation induced by salbutamol. However, the antagonists of Gi protein (PTX) and PDE III (amrinone) showed opposite effects. This study indicates that β2-AR activation increases the incidence of VA in the experimental HF model via activation of Gs/cAMP/PKA and/or inhibition of Gi/PDE pathways.

No MeSH data available.


Related in: MedlinePlus

Effects of β2-AR stimulation on Ikr in myocytes from isolated failing heart.(A) Representative tail traces of IKr inhibited by salbutamol (Sal) in LV myocytes isolated from control (Con, left) and HF guinea pigs (HF, right). (B) Summarized data from decreased percentage of Ikr in control () and HF () myocytes (*p < 0.05, HF vs. Con, n = 6 cells, 6 hearts).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4286790&req=5

f5: Effects of β2-AR stimulation on Ikr in myocytes from isolated failing heart.(A) Representative tail traces of IKr inhibited by salbutamol (Sal) in LV myocytes isolated from control (Con, left) and HF guinea pigs (HF, right). (B) Summarized data from decreased percentage of Ikr in control () and HF () myocytes (*p < 0.05, HF vs. Con, n = 6 cells, 6 hearts).

Mentions: Twelve weeks after aortic constriction, left ventricular myocytes isolated from the hearts of the control and HF groups were used to measure Ikr and APD stimulated by salbutamol by the whole-cell patch-clamp technique (Fig. 5). The mean current densities of Ikr in the control and HF groups were shown in Fig. 5B. The Ikr tail current density in the HF group was significantly decreased by salbutamol compared to control group (36.5 ± 3.35% vs. 22.84 ± 3.97%, n = 6, p < 0.05).


β2 adrenergic receptor activation governs cardiac repolarization and arrhythmogenesis in a guinea pig model of heart failure.

Wang Y, Yuan J, Qian Z, Zhang X, Chen Y, Hou X, Zou J - Sci Rep (2015)

Effects of β2-AR stimulation on Ikr in myocytes from isolated failing heart.(A) Representative tail traces of IKr inhibited by salbutamol (Sal) in LV myocytes isolated from control (Con, left) and HF guinea pigs (HF, right). (B) Summarized data from decreased percentage of Ikr in control () and HF () myocytes (*p < 0.05, HF vs. Con, n = 6 cells, 6 hearts).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4286790&req=5

f5: Effects of β2-AR stimulation on Ikr in myocytes from isolated failing heart.(A) Representative tail traces of IKr inhibited by salbutamol (Sal) in LV myocytes isolated from control (Con, left) and HF guinea pigs (HF, right). (B) Summarized data from decreased percentage of Ikr in control () and HF () myocytes (*p < 0.05, HF vs. Con, n = 6 cells, 6 hearts).
Mentions: Twelve weeks after aortic constriction, left ventricular myocytes isolated from the hearts of the control and HF groups were used to measure Ikr and APD stimulated by salbutamol by the whole-cell patch-clamp technique (Fig. 5). The mean current densities of Ikr in the control and HF groups were shown in Fig. 5B. The Ikr tail current density in the HF group was significantly decreased by salbutamol compared to control group (36.5 ± 3.35% vs. 22.84 ± 3.97%, n = 6, p < 0.05).

Bottom Line: These effects could be prevented by the selective β2-AR antagonist, ICI118551.Salbutamol prolonged APD90 and reduced Ikr in guinea pig HF myocytes.However, the antagonists of Gi protein (PTX) and PDE III (amrinone) showed opposite effects.

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.

ABSTRACT
β2-AR activation increases the risk of sudden cardiac death (SCD) in heart failure (HF) patients. Non-selective β-AR blockers have greater benefits on survival than selective β1-AR blockers in chronic HF patients, indicating that β2-AR activation contributes to SCD in HF. This study investigated the role of β2-AR activation on repolarization and ventricular arrhythmia (VA) in the experimental HF model. The guinea pig HF was induced by descending aortic banding. The effective refractoriness period (ERP), corrected QT (QTc) and the incidence of VA were examined using Langendorff and programmed electrical stimulation. Ikr and APD were recorded by the whole cell patch clamp. Selective β2-AR agonist salbutamol significantly increased the incidence of VA, prolonged QTc and shortened ERP. These effects could be prevented by the selective β2-AR antagonist, ICI118551. Salbutamol prolonged APD90 and reduced Ikr in guinea pig HF myocytes. The antagonists of cAMP (Rp-cAMP) and PKA (KT5720) attenuated Ikr inhibition and APD prolongation induced by salbutamol. However, the antagonists of Gi protein (PTX) and PDE III (amrinone) showed opposite effects. This study indicates that β2-AR activation increases the incidence of VA in the experimental HF model via activation of Gs/cAMP/PKA and/or inhibition of Gi/PDE pathways.

No MeSH data available.


Related in: MedlinePlus