Combination Treatment With Antihypertensive Agents Enhances the Effect of Qiliqiangxin on Chronic Pressure Overload-induced Cardiac Hypertrophy and Remodeling in Male Mice.

Hypertension, which is one of the most common causes of heart failure, reportedly leads to the development of cardiac hypertrophy, which ultimately progresses to heart failure.1,2 Chronic pressure overload–induced adaptive cardiac hypertrophy is initially characterized by a thickened ventricular wall and by enhanced left ventricular systolic function. Excessive activation of the renin–angiotensin–aldosterone system and other neuroendocrine systems, as well as the release of angiotensin II (Ang II) and catecholamines, results in the development of irreversible chronic heart failure.3,4 Despite significant improvements in the understanding of this disease, as well as the effort expended to treat it, the prognosis of heart failure continues to be poor.5,6 Qiliqiangxin (QL) capsules contain a specific traditional Chinese medicine formulation that includes extracts from 11 types of herbs, including Radix Astragali, aconite root, Salvia miltiorrhiza, Ginseng, Semen Lepidii Apetali, Carthamus tinctorius, Cortex Periplocae Sepii Radicis, Rhizoma Alismatis, seasoned orange peel, Polygonatum Odorati, and Rumulus Ginnamomi, based on the meridian theory. Radix astragali is the principal active pharmacological component.7 QL has been demonstrated to be both a safe and efficient treatment for heart failure in both animal models and clinical trials.7–10 In 2004, QL capsules were approved by the Chinese Food and Drug Administration for the treatment of patients with heart failure. Our previous study demonstrated that QL suppressed myocardial inflammation, cardiomyocyte apoptosis, and autophagy while promoting cardiomyocyte proliferation, which resulted in the amelioration of pressure overload–induced cardiac remodeling and cardiac dysfunction.11 Other studies have revealed that QL may improve cardiac dysfunction in spontaneous hypertensive rats by inhibiting the cardiac chymase signaling pathway and that QL may have antiarrhythmic properties that enable it to regulate L-type Ca currents, Na currents, and K currents in rat ventricular myocytes.8,12 According to the 2013 AHA guidelines for the management of heart failure, diuretics, angiotensin-converting enzyme inhibitors (ACEIs), ARBs, beta-blockers, aldosterone receptor antagonists, and other agents are recommended as standard therapies for chronic heart failure.1 However, it is not clear whether combining these drugs with QL can enhance its effects on chronic heart failure. Recently, a multicenter, randomized, double-blind and placebo-controlled study revealed that QL further decreased the level of NT-proBNP in patients with chronic heart failure when used together with standard therapy. These results suggest that QL in combination with standard therapy may represent an improved means of treating chronic heart failure.7 In this study, we treated mice suffering from pressure overload with either QL alone or with QL in combination with olmesartan (ARB), captopril (ACEI) or metoprolol (BB), as each of these drugs is widely prescribed in clinical practice to treat chronic heart failure.13–15 We aimed to determine whether QL combined with these antihypertensive agents exerted superior cardioprotective effects compared with QL alone in the setting of chronic pressure overload–induced cardiac remodeling. We also attempted to determine whether the suppression of cardiomyocyte apoptosis and autophagy as well as the upregulation of cardiomyocyte proliferation as a result of QL treatment were affected by the use of the 3 aforementioned classes of drugs.