Importantly, Venlafaxine together these findings suggest that the cardiac renin-angiotensin system plays an important role in the development of cardiac hypertrophy, fibrosis and heart even if the initiating stimulus of cardiac Gaq activation does not result from AT1 receptor stimulation. It has been shown that mechanical stress activates AT1 receptor independently of angiotensin II, and this activation can be inhibited by an inverse agonist of the AT1 receptor. Our previous study demonstrated that the left Liproxstatin-1 ventricular enddiastolic pressure was increased in Gaq-TG compared with that in NTG mice, suggesting that mechanical stretching of the myocardium was induced in Gaq-TG mice, leading to activation of AT1 receptors. Recent study has demonstrated that olmesartan has strong inverse agonist activities against the constitutively active AT1 receptor and the stretch-induced activation of AT1 receptor, respectively. Therefore, olmesartan induced inhibition of ventricular myocyte hypertrophy and interstitial fibrosis in GaqTG may be caused in part through inverse agonistic action. In this study, chronic administration of olmesartan prevented the progression of heart failure and ventricular arrhythmia in GaqTG mice. In fact, electrocardiogram demonstrated that PVC was frequently observed in 9 of 10 vehicletreated Gaq-TG mice but in none of 10 olmesartan-treated GaqTG mice. In addition, the QT interval was significantly shorter in olmesartan-treated Gaq-TG than in vehicle-treated Gaq-TG mice. Moreover, the MAP duration was also significantly shorter in olmesartan-treated Gaq-TG than in vehicle-treated Gaq-TG mice. It is well known that ventricular arrhythmias are common in heart failure. However, a recent study demonstrated that chronic angiotensin II stimulation in the heart directly induced QT prolongation through down-regulation of potassium channels, which can induce triggered activity, leading to the production of PVC.Moreover, a recent study clearly demonstrated that AT1 receptor signaling in the heart directly contributed to the increased arrhythmogenicity in cardiac hypertrophy. In fact, our previous study demonstrated that early-after depolarization by the prolongation of action potential duration caused triggered activity.