Qili Qiangxin improves heart function in spontaneously hypertensive rats by inhibiting myocardial chymotrypsin

The aim of this study was to investigate the effect of Qiliqiangxin on cardiac function in spontaneously hypertensive rats (SHR) and its mechanism.

We evaluated the effects of oral high doses (4g/kg/ day, n=7) and low doses (1g/kg/ day (n=7)) of Qili Qiangxin on cardiac function in 8-year old SHR rats compared to a control group (8-week-old Wistar-Kyoto (WKY) rats). Echocardiography is used to assess cardiac function and hemodynamic parameters. Hematoxylin-eosin (HE) and Masson tri-color staining were used to evaluate the expression of myocardial angiotensin (Ang) converting enzyme, chymotrypsin, transforming growth factor (TGF-β) and type I and III collagen by real-time reverse transcription polymerase chain reaction. The activities of myocardial chymase, angiotensin-converting enzyme (ACE) and angiotensin II were measured by radioimmunoassay. Cardiac mast cells were detected by toluidine blue staining.

In SHR, the number of chymotrypsin-positive mast cells in the left ventricle (LV) increased compared to WKY rats. Compared with excipients, QLQX significantly reduced mast cell density and cardiac chymotrypsin levels, and improved ejection fraction values and cardiac systolic function. In addition, QLQX reduced the diameter of the left atrium and improved the E/A ratio. QLQX inhibits type I and III collagen, TGF-βmRNA levels, and Ang II activity in a dose-dependent manner. Although no difference was found in ACE activity between SHRS, QLQX significantly reduced the expression and activity of chymotrypsin.

These data suggest that Qili Qiangxin improves systolic and diastolic cardiac function in SHR by down-regulating cardiac chymotrypsin signaling pathways and chymotrypsin-mediated Ang II production.