Department of Pharmacology, L. M. College of Pharmacy, Ahmedabad, Gujarat, India.
Clin Exp Pharmacol Physiol. 2019 Nov;46(11):1037-1043. doi: 10.1111/1440-1681.13143. Epub 2019 Aug 16.
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-RGS2 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-RGS2 signalling inhibitor (1 and 10 mg/kg/d, p.o., 7 days) treated arrhythmic rats. Gαq-RGS2 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-RGS2 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-RGS2 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-RGS2 signalling inhibitor treatment (10 mg/kg) significantly reduced the cAMP level and increased the antioxidant enzyme level as compared to DC. Gαq-RGS2 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.
G 蛋白偶联受体介导的 Gαq 依赖性信号通路的过度激活与心血管异常的发展广泛相关。本研究旨在评估 (1-(5-氯-2-羟基苯基)-3-(4-(三氟甲基)苯基)-1H-1,2,4-三唑-5(4H)-酮) Gαq-RGS2 信号抑制剂对大鼠茶碱诱发心律失常的影响。大鼠分为四组：正常大鼠、疾病对照组（DC，茶碱 100mg/kg/d，腹腔注射，7 天）、Gαq-RGS2 信号抑制剂（1 和 10mg/kg/d，灌胃，7 天）处理心律失常大鼠。从第 1 天开始，在给予茶碱前 1 小时给予 Gαq-RGS2 信号抑制剂。研究结束时，通过麻醉大鼠的心电图（ECG）测量心率（HR）、QRS 复合体、QT 和 RR 间期。通过有创方法测量收缩压（SBP）和舒张压（DBP），测量血清中心肌损伤标志物（CK-MB、LDH）、抗氧化酶（SOD、过氧化氢酶、谷胱甘肽）和 cAMP 水平。与 DC 大鼠相比，Gαq-RGS2 信号抑制剂（10mg/kg）的治疗显著消除了茶碱引起的心率增加、RR 和 QT 间期延长。与 DC 相比，Gαq-RGS2 信号抑制剂（1 和 10mg/kg）显著减轻了 QRS 复合体延长、SBP、DBP 和心肌损伤标志物增加。与 DC 相比，Gαq-RGS2 信号抑制剂（10mg/kg）治疗显著降低了 cAMP 水平并增加了抗氧化酶水平。Gαq-RGS2 信号抑制剂（10mg/kg）对茶碱引起的心律失常显示出保护作用，这可能是由于 cAMP 水平和抗氧化酶的改善。
