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OBJECTIVE Salvianolic acid A (SAA) is one of the most bioactive compounds from a traditional Chinese medicine called Dan Shen(Salvia Miltiorrhiza Bunge)and exhibits many pharmaco-logical activities.Previous studies have indicated that SAA may inhibit endothelial dysfunction and vascular remodeling in spontaneously hypertensive rats. However, whether SAA improves vascular remodeling induced by pulmonary arterial hypertension (PAH) remains unknown. In this study we examined whether SAA attenuated vascular remodeling in a PAH rat induced by monocrotaline(MCT),and elucidated the underlying mechanisms.METHODS PAH was induced in rats by injecting a single dose of monocrotaline (MCT 60 mg·kg-1).The rats were orally treated with either SAA(0.3,1,3 mg·kg-1·d-1)or a positive con-trol Bosentan(30 mg·kg-1·d-1)for 4 weeks.Echocardiography and hemodynamic measurements were performed on d 28.Then the hearts and lungs were harvested,the organ indices and pulmonary artery wall thickness were calculated,and biochemical and histochemical analysis were conducted.The levels of apoptotic and signaling proteins in the lungs were measured using immunoblotting.RESULTS Treatment with SAA effectively ameliorated MCT-induced pulmonary artery remodeling,pulmonary hemodynamic ab-normalities and the subsequent increases of right ventricular systolic pressure (RVSP). Furthermore, the treatments significantly attenuated MCT-induced hypertrophic damage of myocardium,parenchymal in-jury and collagen deposition in the lungs.Moreover,the treatments attenuated MCT-induced apoptosis and fibrosis in the lungs.The treatments partially restored MCT-induced reductions of bone morphoge-netic protein typeⅡ receptor (BMPRⅡ) and phosphorylated Smad1/5 in the lungs. CONCLUSION SAA ameliorates the pulmonary arterial remodeling in MCT-induced PAH rats most likely via activating the BMPRII-Smad pathway and inhibiting apoptosis.Thus,SAA may have therapeutic potential for the pa-tients at high risk of PAH.
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Objective: To observe the effect of aqueous extract from roots of Arctium lappa (AERAL) on vascular remolding in hypertensive rats. Methods: The hypertensive rat model was induced by N-nitro-L-arginine from 50 female Wistar rats, and randomly divided into model control group, positive control group (15 mg/kg), low-, mid-, and high-dose AERAL (0.5, 1.0, and 2.0 g/kg), groups. After six weeks of continuous gavage administration, rat tail artery systolic pressure, angiotensin II (Ang-II), endothelin-1 (ET-1), tumor necrosis factor-α (TNF-α), left ventricular mass index (LVWI), and thickness of thoracic aortic tunica media (TTATM) were detected. Results: Compared with the normal control group, Ang-II, ET-1, TNF-α, LVWI, and TTATM were increased and rat tail artery systolic pressure was elevated in the model control group, with significant differences between the two groups (P < 0.05); Compared with the model control group, rat tail artery systolic pressure in each treatment groups declined, serum Ang-II, ET-1, TNF-α, LVWI, and TTATM were all lowered, showing significant differences among them (P < 0.05). Conclusion: AERAL can significantly improve vascular remolding in rats with hypertension.
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Objective To finding out the characters of vascular remolding after the establishment of native arteriovenous fistula on the wrist,and exploring the influential factors.Methods Doppler ultrasound was used to monitor the diameter of cephalic vein,brachial artery,radial artery and ulnar artery at the time before the surgery and one day,one week,two weeks,four weeks and eight weeks after the surgery respectively.The tendency of the diameter change was analyzed.Results Twenty eight patients completed the whole monitor session,in which eleven were female.The average age of those patients was (53.68 ± 2.61) years old.Twelve of them were diabetic nephropathy.The diameters of all vessel were increased more rapidly at the first day than any other days after surgery(all P ＜ 0.01).The patients were divided into two groups depending on whether diabetic nephropathy.No significant difference was found between the two groups on the tendency of diameter change in cephalic vein and brachial artery (all P ＞ 0.05).However,the tendency of diameter change in radial artery and ulnar artery was statistically significant difference between the two groups (all P ＜ 0.05).Conclusions Cephalic vein,brachial artery,radial artery and ulnar artery are all apparently dilated on the first day after the surgery.The vascular dilation and diameter increasing become much slower after the period,the diameter tend to be stable.The primary diseases may affect the tendency of the diameter change in radial artery as well as ulnar artery.
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Congenital heart disease with left-to-right shunt easily lead to pulmonary hypertension.Currently agreed about its mechanism:shear stress induced by high pulmonary blood flow stimulus pulmonary endothelium,to start regulation of genetic transcription,to initiate a series of molecular biology and pathophysiology changes,and finally to lead to pulmonary vascular pathologic remolding.Nuclear factor(NF)-?B is a kind of nuclear factor with multiple biological effect and play an important role in pulmonary vascular remolding.NF-?B signal can be actiacted by high blood flow.Its target gene products,for example,vasoactive mediators,cytokines,make pulmonary vessels difficulty to maintain the normal structure and cause pulmonary vascular contraction and remolding,thus,pulmonary arterial pressure increases.
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Objective To explore the effect of prenatal inflammation on vascular remolding and blood pressure in mid-aged rats.Methods Time-mated pregnant Sprague-Dawley(SD)rats were randomly divided into 2 groups,received peritoneal injection of 0.79 mg/kg LPS on the gestation days 8,10,and 12,or same volume of the sterile saline at the same time points.Nine pups were randomly selected from each group for the later experiments,and the offspring were named as LPS groups for those having prenatal LPS exposure and control group for those having not.Their blood pressure was determined with a rat tail non-invasive instrument by tail-cuff method from 6 weeks old to 35 weeks old,and then their aortas were taken out for media thickness(MT),diameter of lumen(LD),and the ratios of MT/LD.The expression of proliferating cell nuclear antigen(PCNA)on the vessel was detected by ELISA.The serum level of NO and plasma endothelin-1(ET-1)were measured by nitrate reductase and radioimmunoassay respectively.Results Compared with control group,LPS groups had significantly raised blood pressure,a significantly higher ratio of MT/LD,obviously increased expression of PCNA,and markedly elevated serum ET-1.Conclusion The offspring whose prenatal rats were exposured to LPS result in vascular remolding,vasofunctional disturbances and hypertension.
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Nitric oxide (NO) and matrix metalloproteinases (MMPs) are important in vascular remolding, especially in abdominal aortic aneurysm. NO may be associated with aneurysms by modulating MMPs expression and activity. [
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Hypoxic pulmonary hypertension(HPH) is a common disease featured by acute hypoxic pulmonary vasoconstriction(HPV) and chronic hypoxic pulmonary vascular remolding(HPVR) leading to the sustained increasing of pulmonary artery pressure.There are many mediators involved in the HPH but none can illustrate it successfully.Primary work has found 15-lipoxygenase(15-LO) and its catalyzed production 15-hydroxyeicosatetraenoic acid(15-HETE)(from arachidonic acid) are up-regulated in pulmonary vascular when exprosed to hypoxia.And it has been found 15-LO/15-HETE involved in many processes of both the HPV and HPVR,indicating 15-LO/15-HETE may be an important mediator of HPH.Advances research on 15-LO/15-HETE may illustrate the mechanism of HPH,and will give some message in looking for a potential clinical target of HPH.