Protective effects of Gαq-RGS2 signaling inhibitor in aminophylline induced cardiac arrhythmia.

An over activation of GPCR mediated Gαq dependent signaling 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-RGS2 signaling inhibitor on aminophylline induced cardiac arrhythmia in rats. Rats were divided into four groups; normal rats, disease control (DC, aminophylline treated 100mg/kg/d, i.p., 7 days), Gαq-RGS2 signaling inhibitor (1 and 10mg/kg/d, p.o., 7 days) treated arrhythmic rats. Gαq-RGS2 signaling inhibitor was administered 1 hr prior to the administration of aminophylline from 1 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-RGS2 signaling inhibitor (10mg/kg) significantly abolished the aminophylline induced increase of heart rate, prolongation of RR and QT interval as compared to DC rats. Gαq-RGS2 signaling inhibitor (1 and 10mg/kg) significantly attenuated the prolongation in QRS complex, increase of SBP, DBP and cardiac damage markers as compared to DC. Gαq-RGS2 signaling inhibitor treatment (10mg/kg) significantly reduced the cAMP level and increased the antioxidant enzyme level as compared to DC. Gαq-RGS2 signaling inhibitor (10mg/kg) showed the protective effect against the aminophylline induced cardiac arrhythmia and it might be due to improvement in cAMP level and antioxidant enzymes. This article is protected by copyright. All rights reserved.