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Objective:To evaluate the effect of cinacalcet on right ventricular function in rats with MCT-induced arterial pulmonary hypertension by echocardiography.Methods:Thirty male SD rats were randomly divided into control group, PAH group, and cinacalcet group, with 10 rats in each group. Rats in the cinacalcet group were given intraperitoneal injection of cinacalcet hydrochloride with 30 mg/kg, and the control group and the PAH group were given equal-volume of solvent. Echocardiographic parameters: right ventricular wall thickness (RVWT), right ventricular basal dimension (RVD), left ventricular eccentricity index (EI), tricuspid annular plane systolic excursion (TAPSE), right ventricular fractional area change (RVFAC), tricuspid lateral annular systolic velocity (s′), right ventricular global longitudinal strain (RV4CSL), and right ventricular free wall longitudinal strain (RVFWSL), etc. Histopathological parameters: pulmonary arteriole wall thickness (WT), right ventricular cardiomyocyte mean diameter (RV cell-D), collagen volume fraction (CVF) and right ventricular hypertrophy index (RVI). Echocardiographic and pathological parameters were compared among three groups, and the correlation between right ventricular pathological changes and strain parameters was analyzed.Results:①Compared with the control group, WT, RV cell-D, CVF and RVI in PAH group were increased (all P<0.01), the size of right ventricle and thickness of RV wall were increased (all P<0.05), and the right ventricular longitudinal strain was reduced ( P<0.01). ②Compared with the PAH group, rats in the cinacalcet group showed reduced WT, RV cell-D, CVF and RVI (all P<0.01), as well as improved structure and function of the right ventricle (all P<0.05). There was no statistical difference of the above parameters between cinacalcet and control group (all P>0.05). ③Correlation analysis: the right chamber remodeling parameters CVF and RV cell-D were positively correlated with WT ( rs=0.706 3, 0.629 4; both P<0.05); and RVFWSL correlated well with CVF, RV cell-D ( rs=-0.685 3, r=-0.767 2; both P<0.05). Conclusions:The right ventricular inverse remodeling of PAH rats with the intervention of cinacalcet was retained, suggesting that cinacalcet had a protective effect on the structure and function of the right ventricle in rats with PAH.
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AIM:To investigate regulatory roles of Apelin in adventitial remodeling and fibrosis in rats with transverse aortic constriction ( TAC) .METHODS:The male Sprague-Dawley rats with TAC were randomized to daily deliver either pyroglutamyl Apelin-13 ( 50μg/kg) or saline for 4 weeks.RESULTS:Histomorphometric analysis by HE and Masson Trichrome staining revealed increased medi -al and adventitial thicknesses , especially in the adventitia , in ascending aortas in rats with TAC when compared with the sham-operated rats.Downregulation of APJ receptor and elevations in phosphorylated mTOR and ERK 1/2 levels were observed in rats with TAC . There are marked increases in heart weight ( HW) , HW/body weight ratio , and aortic fibrosis in rats with TAC .The pressure over-load-mediated pathological adventitial remodeling was strikingly rescued by Apelin-13, associated with attenuation of aortic fibrosis and reduced mRNA expression of TGF-β1, fibronectin and collagen I .CONCLUSION:Our results demonstrate the importance of Apelin-13 in amelioration of aortic adventitial remodeling and fibrosis in rats with TAC via modulation of the mTOR /ERK signaling , thus indi-cating potential therapeutic strategies by enhancing Apelin /APJ action for preventing pressure overload-and fibrosis-associated cardio-vascular disorders .
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Objective:To explore the alteration of brain‐derived neurotrophic factor (BDNF) signaling and the influ‐ence of irbesartan on it in hippocampus of angiotensin‐converting enzyme 2 (ACE2) knock‐out (KO) mice . Meth‐ods:The 10~11‐week ACE2 KO (Ace2/y ) mice received daily treatment with angiotensin II (Ang II) type 1 (AT1) receptor blocker irbesartan (50 mg/kg) or placebo for two weeks. The wild‐type mice (WT ,Ace2+ /y ) were regarded as normal control. Western blotting method was used to measure levels of BDNF and extracellular signal regulated kinase 1/2 (ERK1/2) in the mice hippocampus. Radioimmunoassay was used to measure plasma Ang level in mice . Results :Compared with normal WT control mice ,there were significant down‐regulations of BDNF protein expres‐sion [ (1 ± 0.16) vs .(0.54 ± 0.16)] in hippocampus and plasma Ang‐ (1‐7) level [ (55.6 ± 7.5) pg/ml vs .(42.8 ± 5.8) pg/ml] ,and significant rise in ERK1/2 phosphorylation [ (1 ± 0.28) vs .(1.79 ± 0.29)] in ACE2 KO mice (P<0.01 all). After irbesartan treatment ,there were significant rise in BDNF protein expression (0.88 ± 0.13) in hippocampus and plasma Ang‐ (1‐7) level [(59.4 ± 8.4) pg/ml] ,and significant reduction in ERK1/2 phosphoryla‐tion level (1.33 ± 0.19) in ACE2 KO mice (P<0.05 or <0.01) .Conclusion:There are BDNF protein expression down‐regulation and enhanced ERK1/2 phosphorylation in hippocampus of ACE2 KO mice. AT1 receptor blockade irbesartan can improve Ang‐ (1‐7 ) level and hippocampus BDNF expression , while reducing hippocampus ERK phosphorylation signal in ACE2 KO mice ,suggesting that AT1 receptor blockade possesses certain brain protective effect.
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Backgroup and objective Angiotensin-converting enzyme 2 (ACE2) is the first known homologue of human ACE gene up till now,however,its regulatory role in oxidative stress remains unclear.Our aim is to in- vestigate the effects of recombinant ACE2 gene transfer on the expression of p22~(phox),a key subunit of NADPH oxi- dase,and malonyldialdehyde (MDA) levels induced by angiotension(Ang) Ⅱ in cultured human endothelial cells. Methods A recombinant plasmid encompassing human ACE2 gene (pACE2) was constructed and transfected into these cells.The mRNA and protein levels of p22~(phox) in endothelial cells were determined by real-time PCR and Western blotting,respectively.MDA contents were measured by thiobarbiturie acid colorimetrie method in cells. Results The mRNA and protein expressions of p22~(phox) were drastically enhanced after exposures of endothelial cells to Ang Ⅱ(100 nmol/L) and Ang Ⅳ(100 nmol/L),accompanied by an increase in MDA contents (n=6,P
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Aim To investigate changes of MAP2 expression level in rat hippocampal pyramidal cells induced by chronic stress, and to explore effects of tianeptine on them. Methods 25 rats were divided randomly into three groups:Control group,Stress group and Stree-tianeptine group. The forced-swimming was performed to rats in stress group and stress-tianeptine. Using the immunohistochemistry and the computerized image technique, expression levels of phosphorated MAP2 and the number the Positive cells were assayed quantitatively in each group. Results Compared with control group (149.34?1.81), the phosphorated MAP2 average gray degree in pyramidal cells of stress group (144.99?4.40) was significantly lower, that of the stress-tianeptine group (148.84?2.73) was significantly higher than that of stress group; The number of phosphorated MAP2 positive cells in stress group (40.36?1.35) was significantly less compared withthat of control group (42.73?1.56); that of stress-tianeptine group (42.14?1.62) was significantly more than that of stress group. Conclusion It is suggested that tianeptine could inhibit the enhancement of phosphorated MAP2 expression in hippocampal pyramidal cells induced by chronic stress.