Search

Background: Enhancing relaxation of resistance arteries and decreasing oxidative stress by using natural products are potential strategies for prevention and treatment of hypertension., Purpose: This study investigated whether aqueous extract of Moringa oleifera leaves (MOE) could alleviate N ω -nitro-L-arginine-methyl ester (L-NAME)-induced high blood pressure via modulation of vascular function and antioxidant properties., Methods: An experimental hypertensive model was established by administration of L-NAME (50 mg/kg/day) in drinking water to male Wistar rats for 3 weeks. Arterial pressure was measured indirectly by tail-cuff plethysmography and directly via femoral artery catheterization. Vasoreactivity of isolated rat mesenteric arterial bed was determined by the changes in perfusion pressure detected by a pressure transducer. Vascular superoxide anion (O 2 •- ) production was determined by lucigenin-enhanced chemiluminescence. Other biochemical measurements including malondialdehyde (MDA) level, superoxide dismutase (SOD), and catalase (CAT) activities were measured by colorimetric assay., Results: L-NAME-treated rats developed significantly increased blood pressure and heart rate. Concurrent oral treatment with MOE (30 and 60 mg/kg/day) could decrease the high blood pressure and tachycardia in a dose-dependent manner. MOE reduced the impairment of acetylcholine-induced relaxation and decreased the hyperreactivity of adrenergic-mediated contraction in response to periarterial nerve stimulation and phenylephrine in isolated mesenteric arterial beds. In addition, MOE exhibited antioxidant effects in the hypertensive rats, as indicated by suppression of vascular O 2 •- production, decrease of plasma and thoracic aorta MDA levels, and increase of antioxidant activities of SOD and CAT. Moreover, MOE (0.001-0.3 mg) produced a dose-dependent relaxation in methoxamine pre-contracted arterial beds isolated from L-NAME hypertensive rats, which was abolished by endothelium denudation., Conclusion: These findings suggest that the antihypertensive effect of MOE in L-NAME-hypertensive rats may be mediated by alleviating vascular dysfunction and oxidative stress and promoting endothelium-dependent vasorelaxation. MOE may be potentially useful as a natural product against hypertension., (Copyright © 2018 Elsevier GmbH. All rights reserved.)

Purpose: Rice bran protein hydrolysates (RBPH) contain highly nutritional proteins and antioxidant compounds which show benefits against metabolic syndrome (MetS). Increased arterial stiffness and the components of MetS have been shown to be associated with an increased risk of cardiovascular disease. This study aimed to investigate whether RBPH could alleviate the metabolic disorders, arterial stiffening, vascular remodeling, and oxidative stress in rats fed a high-carbohydrate and high-fat (HCHF) diet., Methods: Male Sprague-Dawley rats were fed either a standard chow and tap water or a HCHF diet and 15 % fructose solution for 16 weeks. HCHF rats were treated orally with RBPH (250 or 500 mg/kg/day) for the final 6 weeks of the experimental period., Results: Rats fed with HCHF diet had hyperglycemia, insulin resistance, dyslipidemia, hypertension, increased aortic pulse wave velocity, aortic wall hypertrophy and vascular remodeling with increased MMP-2 and MMP-9 expression. RBPH supplementation significantly alleviated these alterations (P < 0.05). Moreover, RBPH reduced the levels of angiotensin-converting enzyme (ACE) and tumor necrosis factor-alpha in plasma. Oxidative stress was also alleviated after RBPH treatment by decreasing plasma malondialdehyde, reducing superoxide production and suppressing p47 phox NADPH oxidase expression in the vascular tissues of HCHF rats. RBPH increased plasma nitrate/nitrite level and up-regulated eNOS expression in the aortas of HCHF-diet-fed rats, indicating that RBPH increased NO production., Conclusion: RBPH mitigate the deleterious effects of HCHF through potential mechanisms involving enhanced NO bioavailability, anti-ACE, anti-inflammatory and antioxidant properties. RBPH could be used as dietary supplements to minimize oxidative stress and vascular alterations triggered by MetS.

N ω -Nitro-l-arginine methyl ester (l-NAME)-induced hypertension and cardiovascular remodeling are associated with oxidative stress and inflammation. Garcinia mangostana Linn., has been reported to have antioxidant and anti-inflammatory properties. This study investigated whether G. mangostana pericarp extract (GME) could prevent l-NAME-induced hemodynamic alterations, cardiovascular remodeling, oxidative stress and inflammation in rats. Male Sprague-Dawley rats were given 40mg/kg/day of l-NAME in drinking water to induce hypertension, and were simultaneously treated with GME at a dose of 200mg/kg/day. Rats that received l-NAME for five weeks had high blood pressure, left ventricular hypertrophy and thickening of aortic wall. Vascular superoxide production, plasma malondialdehyde (MDA), and plasma tumor necrosis factor alpha (TNF-α) were significantly increased in l-NAME-hypertensive rats (p<0.05). This was consistent with up-regulation of the p47 phox NADPH oxidase subunit and iNOS protein expression in aortic tissues (p<0.05). Low levels of plasma nitric oxide metabolites were observed in l-NAME hypertension. GME prevented the development of hypertension and cardiovascular remodeling induced by l-NAME with reduced oxidative stress and inflammation. These data suggest that GME had a protective effect against l-NAME-induced hypertension and cardiovascular remodeling via suppressing p47 phox NADPH oxidase subunit and iNOS protein expression resulting in enhancing NO bioavailability., (Copyright © 2017 Elsevier GmbH. All rights reserved.)

Oxidative stress has been shown to play an important role in development of vascular dysfunction in diabetes. Protocatechuic acid (PCA) has been reported to exert antioxidant and anti-hyperglycemic activities. Diabetes was induced in male Sprague-Dawley rats by a single intraperitoneal injection of 50 mg/kg streptozotocin (STZ). The rats were maintained in a state of hyperglycemia for 12 weeks. Then, PCA (50 or 100 mg/kg/day) was administered orally or insulin (4 U/kg/day) was subcutaneous injected to the rats for 6 weeks. Blood pressure, vascular responses to vasoactive agents, vascular superoxide production, blood glucose, insulin, malondialdehyde, nitric oxide and antioxidant enzymes were examined. The diabetic rats showed weight loss, insulin deficiency, hyperglycemia, increased oxidative stress, decreased plasma nitric oxide, elevated blood pressure, increased vascular response to phenylephrine and decreased vascular responses to acetylcholine and sodium nitroprusside. PCA significantly decreased blood glucose and oxidative stress, and increased plasma nitric oxide in diabetic rats. Interestingly, PCA treatment restored blood pressure and vascular reactivity, and antioxidant enzyme activity diabetic rats. This study provides the first evidence of the efficacy of PCA in restoring the vascular reactivity of diabetic rats. The mechanism of action may be associated with an alleviation of oxidative stress., (Copyright © 2015 John Wiley & Sons, Ltd.)

Reactive oxygen species (ROS)-induced oxidative stress plays a major role in pathogenesis of hypertension. Antidesma thwaitesianum (local name: Mamao) is a tropical plant distributed in the tropical/subtropical areas of the world, including Thailand. Mamao pomace (MP), a by-product generated from Mamao fruits, contains large amounts of antioxidant polyphenolic compounds. The aim of this study was to investigate the antihypertensive and antioxidative effects of MP using hypertensive rats. For this purpose, male Sprague-Dawley rats were given Nω-nitro-L-arginine methyl ester (L-NAME), an inhibitor of endothelial nitric oxide synthase (eNOS), in drinking water (50 mg/kg) for three weeks. MP extract was orally administered daily at doses of 100 and 300 mg/kg. L-NAME administration induced marked increase in blood pressure, peripheral vascular resistance, and oxidative stress. MP treatment significantly prevented the increase in blood pressure, hindlimb blood flow and hindlimb vascular resistance of L-NAME treated hypertensive rats (p < 0.05). The antihypertensive effect of MP treatment was associated with suppression of superoxide production from carotid strips and also with an increase in eNOS protein expression and nitric oxide bioavailability. The present results provide evidence for the antihypertensive effect of MP and suggest that MP might be useful as a dietary supplement against hypertension.

Oxidative stress plays a role in maintaining high arterial blood pressure and contributes to the vascular changes that lead to hypertension. Consumption of polyphenol-rich foods has demonstrated their beneficial role in the prevention and treatment of hypertension. Curcumin (CUR), a phenolic compound present in the rhizomes of turmeric, possesses cardiovascular protective, anti-inflammatory and antioxidant properties. The present study was designed to investigate the protective effect of CUR on 2kidney-1clip (2K-1C)-induced hypertension, endothelial dysfunction, vascular remodeling and oxidative stress in male Sprague-Dawley rats. Sham operated or 2K-1C rats were treated with CUR at a dose of 50 or 100 mg/kg/day (or vehicle). After 6 weeks of treatment, CUR ameliorated hemodynamic performance in 2K-1C hypertensive rats (P< 0.05), by reducing blood pressure, increasing hindlimb blood flow and decreasing hindlimb vascular resistance. Hemodynamic restoration was associated with a reduction in plasma angiotensin converting enzyme level. Endothelium-dependent vasorelaxation, in response to acetylcholine, of aortic rings isolated from 2K-1C hypertensive rats-treated with CUR was significantly increased (P< 0.05). CUR also attenuated hypertension-induced oxidative stress and vascular structural modifications. These effects were associated with elevated plasma nitrate/nitrite, upregulated eNOS expression, downregulated p47phox NADPH oxidase and decreased superoxide production in the vascular tissues. The overall findings of this study suggest the mechanisms responsible for the antihypertensive action of CUR in 2K-1C hypertension-induced endothelial dysfunction and vascular remodeling involve the improvement NO bioavailability and a reduction in oxidative stress., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Morus alba Linn. (MA), mulberry leaves have been used as a beverage for prevention of various diseases including hyperlipidemia and hyperglycemia. Recently, the antioxidant activities of the MA leaf extract have been reported. The objective of this study was to investigate the effect of the MA leaf extract on free radical-induced cellular injury. In the in vitro models, the extract scavenged stable free radical (1, 1-diphenyl-2-picrylhydrazyl; DPPH) in a concentration-dependent manner with an IC(50) of 20.10 ± 0.78 μ g/ml. The extract protected the erythrocytes from free radical (2, 2'-azobis (2-amidinopropane) dihydrochloride; AAPH)-induced hemolysis with an IC(50) of 74.22 ± 9.87 μg/ml. Additionally, the extract significantly prevented the gastric mucosal injury induced by ischemia-reperfusion (I/R) in rats when given orally at doses of 0.25 and 0.50 g/kg/day for 3 consecutive days (p < 0.05; n=7). However, this effect was not found when the higher doses (1 and 2 g/kg/day) of the extract were tested. In conclusion, these results indicate that the MA leaf extract possesses the cytoprotective activity against free radical-induced cell injury. Therefore, when given at the appropriate dose range, the mulberry leaf may potentially be used as a food supplement in patients with certain diseases in which the oxidative stress-induced cellular injury is pathologically involved.

Quercetin, a dietary antioxidant flavonoid, possesses strong anti-inflammatory and cytoprotective activities. The effects were investigated in an animal model of lipopolysaccharide (LPS)-induced endotoxaemia and vascular dysfunction in vivo. Male ICR mice were injected with LPS (10 mg/kg; i.p.). Quercetin (50 or 100 mg/kg) was intragastrically administered either before or after LPS administration. Fifteen hours after LPS injection, mice were found in endotoxaemic condition, as manifested by hypotension, tachycardia, and blunted vascular responses to vasodilators and vasoconstrictor. The symptoms were accompanied by increased aortic iNOS protein expression, decreased aortic eNOS protein expression, marked suppression of cellular glutathione (GSH) redox status, enhanced aortic superoxide production, increased plasma malodialdehyde and protein carbonyl, and elevated urinary nitrate/nitrite. Treatment with quercetin either before or after LPS preserved the vascular function, as blood pressure, heart rate, vascular responsiveness were restored to near normal values, particularly when quercetin was given as a preventive regimen. The vascular protective effects were associated with upregulation of eNOS expression, reduction of oxidative stress, and maintained blood GSH redox ratio. Overall findings suggest the beneficial effect of quercetin on the prevention and restoration of a failing eNOS system and alleviation of oxidative stress and vascular dysfunction against endotoxin-induced shock in mice.

Oxidative stress is implicated in various pathological conditions, including septic shock, and other diseases associated with local or systemic inflammation. Curcumin, a major component from turmeric (Curcuma longa), possesses diverse anti-inflammatory, anti-tumour and antioxidant properties. The aim of this study was to investigate the effect of curcumin on modulation of vascular dysfunction and oxidative stress induced by lipopolysaccharide (LPS) in mice. Male ICR mice were treated with curcumin (50 or 100 mg/kg), administered intragastrically, either before or after intraperitoneal injection of LPS (10 mg/kg). Fifteen hours after LPS administration, arterial blood pressure was measured and vascular response to vasoactive agents were assessed. Aortic tissues and blood samples were taken for assays of antioxidant and oxidative stress markers. LPS caused marked hypotension, tachycardia and vascular hyporeactivity. The mean arterial pressures in responses to phenylephrine, acetylcholine, and sodium nitroprusside of LPS-treated mice were significantly decreased when compared with the untreated controls. Curcumin modulated heart rate and restored arterial blood pressure in a dose-dependent manner in both protectively- and therapeutically-treated regimens. Furthermore, the vascular responsiveness of LPS-treated mice was improved by curcumin. Interestingly, the improvements of haemodynamics and vascular response during endotoxaemia were related to alleviation of oxidative stress by reducing aortic-derived superoxide production, suppression of lipid peroxidation and protein oxidation, and decrease in urinary nitric oxide metabolites with preservation of the ratio of glutathione/glutathione disulfide. This study provides the first evidence for the potential role of curcumin in prevention and treatment of vascular dysfunction in mice with endotoxaemia elicited by LPS.

Oxidative stress is a major contributor to the development of vascular dysfunction found in various pathological conditions. Quercetin, one of the potent antioxidant bioflavonoid compounds, has been shown to alleviate oxidative injury by modulation of gene expression leading to suppression of production of reactive oxygen and nitrogen species and conferring an antiapoptotic activity. The aim of the present study was to investigate the protective effects of quercetin in a model of phenylhydrazine (PHZ)-induced oxidant stress, vascular dysfunction and hemodynamic disturbance in rats. Male Sprague-Dawley rats were administered quercetin orally (25 or 50mg/kg/day) for 6 days. On day four, all animals except those in the normal control group, were administered PHZ intraperitoneally. The results showed that PHZ induced severe hemolysis. The mean arterial pressure and hindlimb vascular resistance of PHZ-control rats were markedly decreased compared to normal controls. Treatment with quercetin significantly improved arterial blood pressure and peripheral vascular resistance. Vascular responsiveness to bradykinin, acetylcholine, and phenylephrine in PHZ-control rats was dramatically suppressed and quercetin restored these responses in a dose-dependent manner. Quercetin partially protected blood glutathione, suppressed plasma malondialdehyde levels, and largely suppressed nitric oxide metabolites and superoxide anion production. These results provide the first evidence for the role of the flavonoid, quercetin, in the alleviation of vascular dysfunction in an animal model of PHZ-induced oxidant stress.

Introduction: Diabetic nephropathy (DN) is an important microvascular complication of uncontrolled diabetes. The features of DN include albuminuria, extracellular matrix alterations, and progressive renal insufficiency. Rice bran protein hydrolysates (RBPs) have been reported to have antihyperglycemic, lipid-lowering, and anti-inflammatory effects in diabetic rats. Our study was to investigate the renoprotective effects of RBP in diabetic animals and mesangial cultured cells.Methods: Eight-week-old male db/m and db/db mice were orally treated with tap water or RBP (100 or 500 mg/kg/day) for 8 weeks. At the end of the experiment, diabetic nephropathy in kidney tissues was investigated for histological, ultrastructural, and clinical chemistry changes, and biomarkers of angiogenesis, fibrosis, inflammation, and antioxidant in kidney were analyzed by Western blotting. Protection against proangiogenic proteins and induction of cytoprotection by RBP in cultured mesangial cells was evaluated.Results: RBP treatment improved insulin sensitivity, decreased elevated fasting serum glucose levels, and improved serum lipid levels and urinary albumin/creatinine ratios in diabetic mice. RBP ameliorated the decreases in podocyte slit pore numbers, thickening of glomerular basement membranes, and mesangial matrix expansion and suppressed elevation of MCP-1, ICAM-1, HIF-1α, VEGF, TGF-β, p-Smad2/3, and type IV collagen expression. Moreover, RBP restored suppressed antioxidant Nrf2 and HO-1 expression. In cultured mesangial cells, RBP inhibited high glucose-induced angiogenic protein expression and induced the expression of Nrf2 and HO-1.Conclusion: RBP attenuates the progression of diabetic nephropathy and restored renal function by suppressing the expression of proangiogenic and profibrotic proteins, inhibiting proinflammatory mediators, and restoring the antioxidant and cytoprotective system. [ABSTRACT FROM AUTHOR]

N ω -Nitro- l -arginine methyl ester ( l -NAME)-induced hypertension and cardiovascular remodeling are associated with oxidative stress and inflammation. Garcinia mangostana Linn., has been reported to have antioxidant and anti-inflammatory properties. This study investigated whether G. mangostana pericarp extract (GME) could prevent l -NAME-induced hemodynamic alterations, cardiovascular remodeling, oxidative stress and inflammation in rats. Male Sprague-Dawley rats were given 40 mg/kg/day of l -NAME in drinking water to induce hypertension, and were simultaneously treated with GME at a dose of 200 mg/kg/day. Rats that received l -NAME for five weeks had high blood pressure, left ventricular hypertrophy and thickening of aortic wall. Vascular superoxide production, plasma malondialdehyde (MDA), and plasma tumor necrosis factor alpha (TNF-α) were significantly increased in l -NAME-hypertensive rats ( p < 0.05). This was consistent with up-regulation of the p47 phox NADPH oxidase subunit and iNOS protein expression in aortic tissues ( p < 0.05). Low levels of plasma nitric oxide metabolites were observed in l -NAME hypertension. GME prevented the development of hypertension and cardiovascular remodeling induced by l -NAME with reduced oxidative stress and inflammation. These data suggest that GME had a protective effect against l -NAME-induced hypertension and cardiovascular remodeling via suppressing p47 phox NADPH oxidase subunit and iNOS protein expression resulting in enhancing NO bioavailability. [ABSTRACT FROM AUTHOR]

Copyright of Applied Physiology, Nutrition & Metabolism is the property of Canadian Science Publishing and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Oxidative stress has been shown to play an important role in the pathogenesis of diabetesinduced cardiac dysfunction. Protocatechuic acid (PCA) is a phenolic compound, a main metabolite of anthocyanin, which has been reported to display various pharmacological properties. We proposed the hypothesis that PCA exerts cardioprotection in type 1 diabetic (T1DM) rats. T1DM was induced in male Sprague-Dawley rats by a single i.p. injection of 50 mg/kg streptozotocin (STZ) and groups of these animals received the following treatments for 12 weeks: i) oral administration of vehicle, ii) oral administration of PCA at a dose of 50 mg/kg per day, iii) oral administration of PCA at a dose of 100 mg/kg per day, iv) s.c. injection of insulin at a dose of 4 U/kg per day, and v) a combination of PCA, 100 mg/kg per day and insulin, 4 U/kg per day. Metabolic parameters, results from echocardiography, and heart rate variability were monitored every 4 weeks, and the HbA1c, cardiac malondialdehyde (MDA), cardiac mitochondrial function, and cardiac BAX/BCL2 expression were evaluated at the end of treatment. PCA, insulin, and combined drug treatments significantly improved metabolic parameters and cardiac function as shown by increased percentage fractional shortening and percentage left ventricular ejection fraction and decreased low-frequency:high-frequency ratio inT1DM rats. Moreover, all treatments significantly decreased plasma HbA1cand cardiac MDA levels, improved cardiac mitochondrial function, and increased BCL2 expression. Our results demonstrated for the first time, to our knowledge, the efficacy of PCA in improving cardiac function and cardiac autonomic balance, preventing cardiac mitochondrial dysfunction, and increasing anti-apoptotic protein in STZ-induced T1DM rats. Thus, PCA possesses a potential cardioprotective effect and could restore cardiac function when combined with insulin treatment. These findings indicated that supplementation with PCA might be helpful for the prevention and alleviation of cardiovascular complications in T1DM. [ABSTRACT FROM AUTHOR]

Mali-Nil Surin rice bran hydrolysate (MRH) contains highly nutritional proteins and beneficial phenolic compounds. This study investigated an antihypertensive effect of MRH and evaluated the mechanisms mediating this action in N ω -nitro- L -arginine-methyl ester (L -NAME)-induced hypertensive rats. Antihypertensive activity was determined in male rats orally administered with MRH (100 or 300 mg/kg) or enalapril (15 mg/kg) daily together with L -NAME (50 mg/kg/day) in drinking water, for 21 days. Concurrent oral treatment with MRH lowered the high blood pressure in the L -NAME-induced hypertensive rats. MRH treatment improved endothelial function and increased the endothelium-derived hyperpolarizing factor-mediated vasorelaxation in L -NAME hypertensive rats. L -NAME rats treated with MRH had reduced adrenergic hypercontractility, which was associated with a decrease in L -type calcium channel-mediated vasoconstriction. In addition, MRH exhibited antioxidant activity in hypertensive rats, as indicated by suppression of vascular superoxide anion production and reduction of malondialdehyde levels, as well as magnification of superoxide dismutase and catalase activities in serum. This study demonstrated the nutraceutical potential of MRH to prevent oxidative stress-related vascular dysfunction in hypertension. [Display omitted] • Continuous oral treatment of L -NAME hypertensive rats with Mali-Nil Surin rice bran hydrolysate (MRH) lowers high blood pressure by decreasing oxidative stress, endothelial dysfunction, and adrenergic hypercontractility. • MRH treatment decreases oxidative stress through suppression of vascular ROS production and lipid peroxidation as well as enhancement of antioxidant enzyme activity. • MRH alleviates endothelial dysfunction most probably through a decreased impairment of EDHF-mediated endothelium-dependent vasorelaxation. • MRH alleviates adrenergic hypercontractility which is partially dependent on reduction of the increased L -type Ca2+ channels-mediated response. [ABSTRACT FROM AUTHOR]