Role of eNOS/PKG-1 pathway in L-Arginine against right ventricular remodeling induced by monocrotaline in rats / 中国药理学通报

Aim To investigate the role of eNOS/PKG- 1 pathway in L-arginine (L-arg) intervention in right ventricular remodeling induced by monocrotaline (MCT) in Sprague Dawley (SD) rats with the aid of the tool medicine L-NAME. Methods Twenty SD rats were randomly divided into control group, MCT group, L-Arg group and L-Arg + L-NAME group. The general condition of rats was observed; the right ventricular pressure of rats was measured by right heart catheterization; the rats and the right ventricle were weighed and the right ventricular mass index was calculated; the morphological changes of the right ventricular were observed by H&E staining; the protein expressions of cTnl, eNOS and PKG-1 were detected by Western blot in the right ventricular. Results Compared with control group, right ventricular max pressure and right ventricular mass index significantly increased ( P < 05) ; the weight of rats in MCT group was significantly reduced ( P < 0. 05); the right ventricular myocytes were hypertrophic, disordered and infiltrated with inflammatory cells; the protein expression of cTnl was obviously up-regulated ( P < 0. 05 ) ; the protein expressions of eNOS and PKG-1 were significantly down- regulated ( P < 0. 05 ) . L-arg could significantly improve the above changes ( P < 0. 05 ). However, the effects of L-arg were inhibited by eNOS inhibitor L- NAME. Conclusions L-arg can improve the right ventricular remodeling in rats induced by MCT, and the mechanism may be related to the up-regulation of the protein levels of eNOS and PKG-1.

Prevention of the Right Ventricular Remodeling by Epalrestat in Pulmonary Arterial Hypertension Rats and the Underlying Mechanisms / 中国药学杂志

OBJECTIVE: To investigate the protective effect of epalrestat on right ventricular remodeling in a rat model of monocrotaline-induced pulmonary arterial hypertension(PAH). METHODS: PAH rats were induced by a single injection of monocrotaline(60 mg·kg-1, sc) and were administered epalrestat(50 or 100 mg·kg-1) for 4 weeks. At the end of experiment, the right ventricular systolic pressure(RVSP) and mean pulmonary artery pressure(mPAP) were monitored via the right jugular vein catheterization into the right ventricle. Right ventricle(RV) and left ventricle(LV)+septum(S) were isolated and weighed, and ratios of RV/(LV+S)and RV to tibial length were calculated. Right ventricular morphological change was observed by HE staining. Masson's trichrome stain was used to demonstrate collagen deposition. The total antioxidative capacity(T-AOC) and malondialdehyde(MDA) levels in right ventricle were determined according to the manufacturer's instructions. The expression of collagen I, collagen III, AR and NOX4 were analyzed by immunohistochemisty, real-time PCR or Western blot. RESULTS: The results showed that epalrestat treatment for 4 weeks attenuated RVSP, mPAP and right ventricular remodeling index(RV/LV+S and RV/Tibial length) of PAH rats induced by monocrotaline. Furthermore, monocrotaline-induced right ventricular collagen accumulation and collagen I and collagen III expression were both significantly suppressed by epalrestat. The expressions of AR, NOX4 and MDA content were obviously decreased, while the T-AOC was significantly increased in right ventricular from PAH rats with epalrestat treatment. CONCLUSION: These results suggest that epalrestat ameliorates right ventricular remodeling of PAH induced by monocrotaline in rats through its down-regulating of AR and NOX4 expression and collagen accumulation.

Effects of atorvastatin on serum levels of inflammatory factors, pulmonary function and right ventricular remodeling in patients with chronic obstructive pulmonary disease complicated with pulmonary hypertension / 药物评价研究

Objective To investigate the effect of atorvastatin on serum levels of inflammatory cytokines,pulmonary function and right ventricular remodeling in patients with chronic obstructive pulmonary disease (COPD) complicated with pulmonary hypertension.Methods From December 2013 to December 2016,106 patients with COPD complicated with pulmonary hypertension were randomly divided into treatment and control groups,each with 53 cases.Patients in control group were treated with routine basic therapy for three months,and patients in treatment group were treated with atorvastatin on the basis of control group.The pulmonary function,right ventricular remodeling function and inflammatory factors were detected,and the clinical efficacy of two groups was evaluated.Results The total effective rate was 94.34％ in the treatment group and 79.25％ in the control group,difference between the two groups was significant (P ＜ 0.05).The levels of FEV1 and FVC were not significantly different between two groups before treatment.The levels of FVC and FEV1 in treatment group were significantly higher than those in the control group after treatment (P ＜ 0.05).After treatment,the LVED,LVPW,TRVmax and RVEF of treatment group were significantly higher than those of control group (P ＜ 0.05),and the difference was statistically significant.Compared with before treatment,LVID,LVPW and TRVmax were increased,RVAD decreased,and the difference was statistically significant (P ＜ 0.05).The levels of CRP,ET and IL-6 in the treatment group were significantly lower than those in the control group (P ＜ 0.05),and difference was statistically significant.Conclusion The effect of atorvastatin on serum inflammatory factors,pulmonary function and right ventricular remodeling in patients with COPD combined with pulmonary hypertension is significant and can be popularized.

Histological changes of the right ventricular remodeling in Xinjiang Marmota baibacina adapted to high-altitude hypoxia / 中国实验动物学报

Objective To investigate the histological changes of the right ventricular remodeling in Xinjiang Mar-mota baibacina which are adapted to high-altitude hypoxia .Methods Hematoxylin and eosin and Masson staining was used to examine the pathological changes and degree of fibrosis , and immunohistochemical technique was used to detect connexin 43 ( CX43) expression in the right ventricular myocardium .Results In the right ventricular myocardium , cardio-myocyte hypertrophy and increased amount of collagen fibers were observed .The right ventricular hypertrophy index and weight index of Marmota baibacina were significantly higher , and expression of CX43 was significantly reduced than that of normal rats ( P<0.05 for both ) .Conclusions High-altitude hypoxia induces right ventricular remodeling in Xinjiang Marmota baibacina.It can be used as an ideal animal model for studies on the mechanisms of hypoxia adaptation on high -altitude plateau .