Protective effects of Gαq‐ RGS RGS 2 signalling inhibitor in aminophylline induced cardiac arrhythmia

摘要

Abstract An over activation of GPCR mediated Gαq dependent signalling pathway is widely associated with the development of cardiovascular abnormalities. The objective of study was to evaluate the effects of (1‐(5‐chloro‐2‐hydroxyphenyl)‐3‐(4‐(trifluoromethyl)phenyl)‐1H‐1,2,4‐triazol‐5(4H)‐one) Gαq‐ RGS 2 signalling inhibitor on aminophylline induced cardiac arrhythmia in rats. Rats were divided into four groups; normal rats, disease control ( DC , aminophylline treated 100?mg/kg/d, i.p., 7?days), Gαq‐ RGS 2 signalling inhibitor (1 and 10?mg/kg/d, p.o., 7?days) treated arrhythmic rats. Gαq‐ RGS 2 signalling inhibitor was administered 1?hour prior to the administration of aminophylline from 1st day. At the end of study, heart rate ( HR ), QRS complex, QT and RR interval were measured by electrocardiogram ( ECG ) of anesthetized rats. Systolic and diastolic blood pressure ( SBP , DBP ) by invasive method, cardiac damage markers ( CK ‐ MB , LDH ) in the serum, antioxidant enzymes ( SOD , catalase, glutathione) and cAMP level were measured. The treatment of Gαq‐ RGS 2 signalling inhibitor (10?mg/kg) significantly abolished the aminophylline induced increase of heart rate, prolongation of RR and QT interval as compared to DC rats. Gαq‐ RGS 2 signalling inhibitor (1 and 10?mg/kg) significantly attenuated the prolongation in QRS complex, increase of SBP , DBP and cardiac damage markers as compared to DC . Gαq‐ RGS 2 signalling inhibitor treatment (10?mg/kg) significantly reduced the cAMP level and increased the antioxidant enzyme level as compared to DC . Gαq‐ RGS 2 signalling inhibitor (10?mg/kg) showed the protective effect against the aminophylline induced cardiac arrhythmia and it might be due to improvement in cAMP level and antioxidant enzymes.