Arterioles Of Mesentery Research Articles

Deep Sea Water-Dissolved Organic Matter Intake Improves Hyperlipidemia and Inhibits Thrombus Formation and Vascular Inflammation in High-Fat Diet Hamsters.

Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease caused by oxidative stress, inflammation and lipid deposition within liver cells, and is subsequently contributing to cardiovascular diseases such as atherosclerosis. Deep sea water (DSW) is characterized by its clearance and abundant nutrients with antioxidant and anti-inflammatory activity to confer therapeutic potential. We aimed to explore the therapeutic capability of our prepared multi-filtration DSW-dissolved organic matter (DSW-DOM) on high-fat diet-induced hyperlipidemia and endothelial dysfunction in hamsters. A high-fat/high-cholesterol diet led to increased oxidative stress, including blood reactive oxygen species (ROS), plasma malondialdehyde (MDA) and hepatic CYP2E1 expression; an increased hyperlipidemic profile and SREBP 1-mediated fatty liver; promoted NFκB p65-mediated hepatic inflammation; triggered PARP-mediated hepatic apoptosis; and enhanced endothelial intercellular adhesion molecule-1 (ICAM-1) and von Willebrand factor (VWF)-mediated atherosclerosis associated with the depressed hepatic antioxidant Paraoxonase 1 (PON1) expression. The DSW-DOM-enriched 1295 fraction, with strong H2O2 scavenging activity, efficiently reduced several oxidative stress parameters, the lipid profile, inflammation, and apoptosis, possibly through the PON1-mediated antioxidant capability. Furthermore, DSW-DOM treatment significantly decreased the endothelial ICAM-1 and VWF expression, subsequently leading to the elongation of time to occlusion of FeCl3-induced arterial thrombosis and to the inhibition of FeCl3-induced fluorescent platelet adhesion to mesentery arterioles in the high-fat diet. Based on the above results, our data suggest that DSW-DOM intake via antioxidant defense mechanisms confers protective effects against high-fat diet-enhanced, oxidative stress-mediated hyperlipidemia, and endothelial dysfunction evoked atherosclerosis by downregulating oxidative injury, lipogenesis, inflammation and apoptosis.

Fluid shear stress regulates placental growth factor expression via heme oxygenase 1 and iron

Increased fluid shear stress (FSS) is a key initiating stimulus for arteriogenesis, the outward remodeling of collateral arterioles in response to upstream occlusion. Placental growth factor (PLGF) is an important arteriogenic mediator. We previously showed that elevated FSS increases PLGF in a reactive oxygen species (ROS)-dependent fashion both in vitro and ex vivo. Heme oxygenase 1 (HO-1) is a cytoprotective enzyme that is upregulated by stress and has arteriogenic effects. In the current study, we used isolated murine mesentery arterioles and co-cultures of human coronary artery endothelial cells (EC) and smooth muscle cells (SMC) to test the hypothesis that HO-1 mediates the effects of FSS on PLGF. HO-1 mRNA was increased by conditions of increased flow and shear stress in both co-cultures and vessels. Both inhibition of HO-1 with zinc protoporphyrin and HO-1 knockdown abolished the effect of FSS on PLGF. Conversely, induction of HO-1 activity increased PLGF. To determine which HO-1 product upregulates PLGF, co-cultures were treated with a CO donor (CORM-A1), biliverdin, ferric ammonium citrate (FAC), or iron-nitrilotriacetic acid (iron-NTA). Of these FAC and iron-NTA induced an increase PLGF expression. This study demonstrates that FSS acts through iron to induce pro-arteriogenic PLGF, suggesting iron supplementation as a novel potential treatment for revascularization.

Effects of Nuclear Factor-E2-related factor 2/Heme Oxygenase 1 on splanchnic hemodynamics in experimental cirrhosis with portal hypertension

ObjectiveWe explored the effects of Nuclear Factor-E2-related factor 2 (Nrf2) and Heme Oxygenase 1 (HO-1) on splanchnic hemodynamics in portal hypertensive rats. MethodsExperimental cirrhosis with portal hypertension was induced by intraperitoneal injection of carbon tetrachloride. The expression of proteins was examined by immunoblotting. Hemodynamic studies were performed by radioactive microspheres. The vascular perfusion system was used to measure the contractile response of mesentery arterioles in rats. ResultsNrf2 expression in the nucleus and HO-1 expression in cytoplasm was significantly enhanced in portal hypertensive rats. Portal pressure, as well as regional blood flow, increased significantly in portal hypertension and can be blocked by tin protoporphyrin IX. The expression of endogenous nitric oxide synthase and vascular endothelial growth factors increased significantly compared to normal rats, while HO-1 inhibition decreased the expression of these proteins significantly. The contractile response of mesenteric arteries decreased in portal hypertension, but can be partially recovered through tin protoporphyrin IX treatment. ConclusionsThe expression of Nrf2/HO-1 increased in mesenteric arteries of portal hypertensive rats, which was related to oxidative stress. HO-1was involved in increased portal pressure and anomaly splanchnic hemodynamics in portal hypertensive rats.

Metformin improves IKCa-mediated endothelial dilative dysfunction of arteriole in diabetic rats

Methods Diabetic rat model was induced by a single intraperitoneal injection of 30 mg/kg STZ after high fat and glucose diet for 8 weeks. Animals whose blood glucose > 11.1 mmol/L were included in diabetic and metformin group. Agematched animals fed with standard chow and injected with citric acid buffer were served as control. Four weeks after STZ injection, rats in three groups were fed with normal diet for additional 8 weeks. After that, fasting blood was drawn and third-order mesenteric arteries were separated. Hemoglobin A1c (HbA1c) was measured with an automatic analyzer. The changes of Achand NS309 (opener of IKCa and small conductance Ca -activated K channel, SKCa) -induced vasodilatation mediated by IKCa in mesentery arterioles of each group and mesentery arterioles of normal rats incubated with 200 μg/mL AGE-BSA (200 μg/mL BSA as control) for 3 hours were measured by multi-myograph system. The effect of metformin on AGEBSA (200 μg/mL) and H2O2 (100 μmol/L) induced changes of IKCa mRNA and protein expression in cultured human umbilical vein endothelial cells (HUVECs) were detected by RT-PCR and Western blot. The level of malondialdehyde (MDA) and the activity of Cu-Zn superoxide dismutase (Cu-Zn SOD) in cellular supernatant were determined by colorimetric method. Results Increased HbA1c level and reduceded endotheliumdependent dilative response mediated by IKCa in mesentery arterioles were observed in diabetic rats, and metformin treatment (300 mg/kg/day by gavage) restored the adverse condition. The vasodilatation mediated by IKCa was also impaired in 200 μg/mL AGE-BSA-incubated mesentery arterioles. AGE-BSA at 200 μg/mL concentration and H2O2 (100 μmol/L) significantly decreased the mRNA and protein expression of IKCa. AGE-BSA also increased the production of MDA and inhibited Cu-Zn SOD activity in HUVECs. Metformin of 10 mol/L and 10 mol/L reversed those effects.

Ingestion of cocoa ameliorates endothelial dysfunction in mesentery arterioles induced by high fat diet in rats: An in vivo intravital microscopy study

Aims:Numerous clinical studies have reported that ingestion of cocoa has a therapeutic effect on hypertension. However, there is only limited information on the mechanism of ingestion of cocoa on arterioles, vessels that have a major role in determining blood pressure. In this study, we used intravital video-microscopy to evaluate the effect of cocoa consumption on the mesentery microcirculation of rats fed a high fat diet.Main methods:The animals were allocated to 3 groups, and fed either a control diet, a high fat diet containing 15% lard, or the HFD with 2% cocoa (HFD-C) for 6weeks. At the end of the experimental period, the mesentery was spread in a chamber, and the vessels were treated topically with phenylephrine, acetylcholine, or papaverine. The vascular responses to phenylephrine, acetylcholine-dependent vasodilatation and endothelium-independent vasodilatation were calculated by the diameter of the mesentery artery with each treatment.Key findings:Topical treatment of mesenteric arterioles with acetylcholine caused a significantly greater response in the control compared with the HFD group. In the HFD-C group, acetylcholine-dependent vasodilatation was decreased marginally. Similarly, rats in the HFD group showed a significant reduction in vascular sensitivity to phenylephrine compared with the control group. However, there was no significant difference between the control and HFD-C groups. The induction of endothelial-independent artery dilation was reduced slightly in the HFD group.Significance:Our results suggest that one of the hypotensive mechanisms of cocoa is due to amelioration of endothelial dysfunction in arterioles induced by an inappropriate diet.

高精度PIV手法による微小血管内流場の解析

Since endothelial cells are subject to flow shear-stress, it is important to determine the fine velocity distribution in microvessels for studies of mechanical interactions between blood and endothelium. Recently, particle image velocimetry (PIV) is a quantitative method of measuring velocity fields instantaneously in experimental fluid mechanics. The authors have been developed a high-resolution PIV technique, which can improve the dynamic range, spatial resolution and measurement accuracy, and applied it to visualized images in a blood flow.In this paper, the proposed method is applied to visualized images in micro tube using an intravital-microscope and high-speed digital video system in order to assess measurement accuracy. The obtained velocity profile corresponds to a theoretical value. Then the micro PIV system is applied to a blood flow of straight tube in rat mesentery arterioles.

Adaptation of Flow-Induced Dilation of Arterioles to Daily Exercise

We aimed to test the hypothesis that daily exercise elicits an adaptation of blood flow/shear stress-induced dilation of arterioles. To this end we investigated the responses of isolated, pressurized arterioles of mesentery (MES) and plantaris (PL) skeletal muscle of sedentary (SED) and exercised (EX) rats to increases in perfusate flow (PF, range 0–30 μl/min). Rats were run on a treadmill, once daily for 3 to 4 weeks (with gradually increasing intensity up to 40 min at 28 m/min; a total of 15–19 sessions on the treadmill). The passive diameters of arterioles (obtained in Ca2+-free solution) were similar (∼140 μm) but the pressure-induced active diameter (at 80 mmHg) of skeletal muscle arterioles was significantly smaller than that of mesenteric arterioles. The basal diameter of MES arterioles of SED and EX rats was: 83.5 ± 3.6 and 83.9 ± 2.9 μm, respectively; increases in PF increased the diameter of SED and EX arterioles to a similar degree by 33.2 ± 4.7 and 31.9 ± 6.1 μm, respectively). The diameters of PL muscle arterioles of SED and EX rats were 62.1 ± 6.2 and 68.0 ± 5.5 μm. In contrast to arterioles of MES, the highest PF increased the diameters of arterioles of PL muscle from EX rats to a significantly greater extent than those from SED rats (52.4 ± 7.8 vs 30.3 ± 3.9 μm). Thus, there is a functional adaptation to exercise activity in arterioles of skeletal muscle but not in those of arterioles of mesentery. We speculate that the intermittent increase in blood flow/shear stress in arterioles of skeletal muscle during the periods of exercise activity may be the underlying mechanism responsible for this adaptation.

Vascular resistance of arterioles with nonuniform diameters

Arterioles in various vascular beds have been often observed to have nonuniform diameters along the vessel axis. The effect of nonuniformity of arteriolar diameter on vascular resistance was investigated using a theoretical model of blood flow in arterioles. Viscous flow of a Newtonian fluid in tubes with periodically changing diameters along the tube axis was analyzed by a finite element method based on the Stokes equations. Vascular resistance for the nonuniform tube was computed over a spatial period of the variation in diameter and was compared to resistance for a uniform tube with a constant diameter equal to the mean diameter of the nonuniform tube. In all cases, resistance for a tube with a nonuniform diameter was larger than resistance for a uniform tube with a diameter equal to the mean diameter of the nonuniform tube. Increases in the amplitude of the variation in diameter resulted in a rapid increase in resistance when the period of the variation remained constant. On the other hand, as the period of the diameter variation increased when amplitude remained constant, resistance decreased and approached the values obtained under the assumption of a Poiseuille flow at each cross section of the tube in the limit of an infinite period. Our theoretical model was applied to our previous in vivo studies of vessel diameter nonuniformity for rabbit mesentery arterioles in a contracted state. It was shown that vascular resistance calculated by our model was 2 to 11% higher than resistance obtained for a uniform tube with a diameter equal to the mean diameter of the arteriole.

Response of the mesenteric microcirculation of rats with experimental renal hypertension to histamine and adrenalin

Reactions of the blood flow and of the diameter of mesentery arterioles were studied in vivo after the application of histamine (100--500 gamma) and adrenaline (1--10 gamma) in normal rats and in the animals with renal hypertension. A decrease of sensitivity of the microvessels, 10--30 mu in diameter, to the action of these substances was shown in the animals with hypertension.