Abstract
Tianma Gouteng Decoction (TGD) is widely used in traditional Chinese medicine for the treatment of hypertension and its related complications, but its mechanisms remain incompletely defined. We now aim to assess the protective effect of TGD against cardiovascular damage and to investigate its characteristics and underlying mechanisms. Blood pressure was determined in TGD-treated spontaneously hypertensive rats (SHR) by noninvasive measurements. Echocardiography was performed to assess cardiac function and structure and sirius red staining to evaluate cardiac fibrosis, and the degree of vascular remodeling was evaluated. Additionally, vasoconstriction and relaxation factor expression changes were examined by means of ELISA. Protein expression changes were verified by western blot. Compared with untreated SHR, TGD-treated SHR exhibited cardiovascular traits more akin to those of the normotensive Wistar Kyoto (WKY) rats. That is, they had lower diastolic blood pressure, systolic blood pressure and mean BP, and increased expression of vasodilation factor. We also found that TGD reduces ventricular and vascular remodeling and improves cardiac function in SHR. Finally, we tested the antiapoptosis effect TGD exerts in SHR, ostensibly by upregulating the expression of OPG, TRAIL, and death receptor 5 (DR5) and downregulating caspases 8, 7, and 3. TRAIL may also exert antiapoptotic and prosurvival effects by upregulating AKT expression. Therefore, TGD may reverse cardiovascular remodeling in SHR by upregulating the expression of OPG and TRAIL, upregulating AKT, and inhibiting apoptosis, at least in part. For the first time, we have shown that OPG and TRAIL play complimentary cardioprotective roles in SHR.
Highlights
Hypertension is a major public health issue worldwide, but the rates of treatment and control are still very low [1]
After 12 weeks of administration of Tianma Gouteng Decoction (TGD), the TGD intervention groups (20 g/kg/d, 40 g/kg/d) had reduced systolic blood pressure (Figure 1(a)), diastolic blood pressure (Figure 1(b)), and mean arterial pressure (Figure 1(c)) compared with the spontaneously hypertensive rats (SHR) + saline group, where TGD at 40 g/kg/d was effective in controlling blood pressure after 8 weeks of administration and 20 g/kg/d was effective after 12 weeks (Figure S1)
Even when TGD has been found to be effective—as in this study—the mechanisms by which it performs its functions remain unclear. is study aimed to evaluate whether TGD resists hypertension by exerting cardiovascular protection via the OPG/tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) system
Summary
Hypertension is a major public health issue worldwide, but the rates of treatment and control are still very low [1]. In recent results from a 1,100,507 participant study in low- and middle-income countries, 192,441 (17.5%) had hypertension; among those with hypertension, 39.2% were newly diagnosed with hypertension and 29.9% of those with hypertension received treatment, but only 10.3% of participants achieved control of their hypertension [2]. Even in high-income countries, the control rate was still less than 25% [3]. It is estimated that one-third of Chinese adults have high blood pressure, and the rate of hypertension control is only 13.0% [4]. In addition to high blood pressure, these cause excessive fibroblast proliferation and increase the accumulation of collagen
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