lignans and Hypertension

A sedentary lifestyle has evoked a high risk of cardiovascular (CV) disease, diabetes, and obesity, all of them with high morbimortality rates and with a common denominator, hypertension. Numerous pharmacological drugs have been used for the treatment of hypertension. However, the side effects associated with the use of existing pharmacological therapies have triggered a demand for plant-based medications. In this connection, the aim of this review was to provide an in-depth analysis of the use of plant-derived bioactives for the effective management of hypertension. Phytoconstituents from leaves, bark, stem, roots, seeds, and fruits of medicinal plants grown in our different regions of the globe have been highly searched. Among them, polyphenols (e.g., flavonoids as quercetin, anthocyanins as cyanidin, tannins as ellagic acid, stilbenes as resveratrol, lignans as honokiol and others as hydroxytyrosol or curcumin), organosulfur compounds (e.g. s-allyl cysteine and allicin), fatty acids (e.g. α-lipoic acid, DHA and oleic acid), alkaloids (e.g. berberine or tetrandrine) and some terpenes have been intensively investigated for the management of hypertension, with effective ability being stated in controlling high blood pressure and related health problems both in vivo and in vitro studies. Some of the activities presented by these bioactive compounds are reducing oxidative stress, renin-angiotensin system control, SIRT1 activation, regulating platelet aggregation and COX activity, anti-atherogenic effects, anti-inflammatory properties, vasorelaxation and other results that translate into the prevention or control of hypertension. The knowledge of these bioactive compounds is important in developing countries where traditional medicine is the majority, but it can also give rise to new approaches in hypertension therapy.

Topics: Anthocyanins; Cardiovascular Diseases; Flavonoids; Humans; Hypertension; Lignans; Plant Extracts; Polyphenols; Resveratrol

Many experimental and clinical trials suggested that flaxseed might be a potent antihypertensive, but the evidences concerning the effects of flaxseed supplements on blood pressure (BP) has not been fully conclusive. We aimed to assess the impact of the effects of flaxseed supplements on blood pressure through systematic review of literature and meta-analysis of available randomized controlled trials (RCTs).. The literature search included PUBMED, Cochrane Library, Scopus, and EMBASE up to February 2015 to identify RCTs investigating the effect of flaxseed supplements on plasma blood pressure. Effect size was expressed as weighed mean difference (WMD) and 95% confidence interval (CI).. 15 trials (comprising 19 treatment arms) with 1302 participants were included in this meta-analysis. Random-effects meta-analysis suggested significant reductions in both systolic BP (SBP) (WMD: -2.85 mmHg, 95%CI: -5.37 to -0.33, p = 0.027) and diastolic BP (DBP) (WMD: -2.39 mmHg, 95%CI: -3.78 to -0.99, p = 0.001) following supplementation with flaxseed products. When the studies were stratified according to their duration, there was a greater effect on both SBP and DBP in the subset of trials with ≥12 weeks of duration (WMD: -3.10 mmHg, 95%CI: -6.46 to 0.27, p = 0.072 and -2.62 mmHg, 95%CI: -4.39 to -0.86, p = 0.003, respectively) vs the subset lasting <12 weeks (WMD: -1.60 mmHg, 95%CI: -5.44 to 2.24, p = 0.413, and -1.74 mmHg, 95%CI: -4.41 to 0.93, p = 0.202, respectively). Another subgroup analysis was performed to assess the impact of flaxseed supplement type on BP. Reduction of SBP was significant with flaxseed powder (WMD: -1.81 mmHg, 95% CI: -2.03 to -1.59, p < 0.001) but not oil (WMD: -4.62 mmHg, 95%CI: -11.86 to 2.62, p = 0.211) and lignan extract (WMD: 0.28 mmHg, 95% CI: -3.49 to 4.04, p = 0.885). However, DBP was significantly reduced with powder and oil preparations (WMD: -1.28 mmHg, 95% CI: -2.44 to -0.11, p = 0.031, and -4.10 mmHg, 95%CI: -6.81 to -1.39, p = 0.003, respectively), but not with lignan extract (WMD: -1.78 mmHg, 95% CI: -4.28 to 0.72, p = 0.162).. This meta-analysis of RCTs showed significant reductions in both SBP and DBP following supplementation with various flaxseed products.

Topics: Antihypertensive Agents; Dietary Supplements; Evidence-Based Medicine; Flax; Humans; Hypertension; Lignans; Linseed Oil; Plant Extracts; Randomized Controlled Trials as Topic; Reproducibility of Results; Seeds

Topics: Acetic Acid; Animals; Antihypertensive Agents; Catechin; Dioxoles; Diterpenes, Kaurane; Docosahexaenoic Acids; Eicosapentaenoic Acid; Functional Food; gamma-Aminobutyric Acid; Garlic; Glucosides; Humans; Hypertension; Lignans; Onions

Sesamin, one of the lignans contained in sesame, has been considered to have medicinal effects. It has been reported that sesamin suppressed the development of hypertension in rats. In this study, using a double-blind, cross-over, placebo-controlled trial, we investigated the effect of 4-wk administration of sesamin on blood pressure (BP) in mildly hypertensive humans. Twenty-five middle-aged subjects with mild hypertension were divided into two groups, matched by age and body mass index. Twelve subjects were allocated to 4-wk intake of capsules with 60 mg sesamin per day and 13 subjects to 4-wk intake of a placebo (period 1). After a 4-wk washout period, the subjects received the alternative administration for 4 wk (period 2). BP decreased with statistical significance with the administration of sesamin (systolic: 137.6+/-2.2 to 134.1+/-1.7 mmHg, p=0.044, diastolic: 87.7+/-1.3 to 85.8+/-1.0 mmHg, p=0.045), but little changed with the placebo (systolic: 135.0+/-1.8 to 135.1+/-1.7 mmHg, diastolic: 85.9+/-1.2 to 86.6+/-1.2 mmHg). In conclusion, 4-wk administration of 60 mg sesamin significantly decreased BP by an average of 3.5 mmHg systolic BP and 1.9 mmHg diastolic BP. These results suggest that sesamin has an antihypertensive effect in humans. Epidemiological studies suggested that a 2-3 mmHg decrease in BP reduces the rate of cardiovascular diseases; therefore, it is considered that BP reduction achieved by sesamin may be meaningful to prevent cardiovascular diseases.

Topics: Antihypertensive Agents; Blood Pressure; Dioxoles; Double-Blind Method; Female; Humans; Hypertension; Lignans; Male; Middle Aged; Phytotherapy; Plant Extracts; Seeds; Sesamum

Sesamin, the major lignan found in sesame, has been shown to increase vitamin E levels by inhibiting its metabolism via the cytochrome P450 isozyme CYP4F2. CYP4F2 and CYP4A11 are the predominant human isoforms that synthesize 20-hydroxyeicosatetraenoic acid (20-HETE) from arachidonic acid. Considerable evidence suggests that 20-HETE may play a role in the pathogenesis of hypertension. We hypothesized that sesamin could be an inhibitor of 20-HETE synthesis. This study investigated the effects of sesamin on 20-HETE synthesis in vitro and the effect of sesame supplementation on plasma and urinary 20-HETE concentrations in humans. Human microsomes were used to investigate the potency and selectivity of sesamin inhibition of 20-HETE synthesis. Sesamin inhibited human renal and liver microsome 20-HETE synthesis with IC50 <20 micromol/L. It was selective toward CYP4F2 (IC50: 1.9 micromol/L) and had reduced activity toward CYP4A11 (IC50: >150 micromol/L), as well as cytochrome P epoxygenation of arachidonic acid (IC50: >50 micromol/L). In a randomized, controlled crossover trial, overweight men and women (n=33) consumed 25 g/d of sesame (approximately 50 mg/d of sesame lignan) or an isocaloric matched control for 5 weeks each. Relative to control, sesame supplementation resulted in a 28% decrease in plasma and a 32% decrease in urinary 20-HETE (P<0.001). Urinary sodium, potassium, and blood pressure were not affected. This study demonstrates for the first time that sesame supplementation in humans reduces the plasma and urinary levels of 20-HETE, likely via inhibition of CYP4F2 by sesame lignans. These results suggest that sesame lignans could be used for the investigation of potential roles of 20-HETE in humans.

Topics: Antihypertensive Agents; Dietary Supplements; Dioxoles; Female; Humans; Hydroxyeicosatetraenoic Acids; Hypertension; In Vitro Techniques; Lignans; Male; Microsomes, Liver; Middle Aged; Plant Extracts; Probability; Reference Values; Treatment Outcome

Although increasing evidence suggests that polyphenol helps regulate blood pressure (BP), evidence from large-scale and long-term population-based studies is still lacking.. This study aimed to investigate the association between dietary polyphenol and hypertension risk in the China Health and Nutrition Survey (N = 11,056).. Food intake was assessed using 3-d, 24-h dietary recalls and household weighing method; polyphenol intake was calculated by multiplying consumption of each food and its polyphenol content. Hypertension was defined as BP ≥ 140/90 mmHg, physicians' diagnosis, or taking antihypertension medications. HR and 95% CI were estimated using mixed-effects Cox models.. During 91,561 person-years of follow-up, a total of 3866 participants developed hypertension (35%). The lowest multivariable-adjusted HR (95% CI) of hypertension risk occurred in the third quartile intake, which was 0.63 (0.57, 0.70) for total polyphenol, 0.61 (0.55, 0.68) for flavonoid, 0.62 (0.56, 0.69) for phenolic acid, 0.46 (0.42, 0.51) for lignan, and 0.58 (0.52, 0.64) for stilbene, compared with the lowest quartile. The polyphenol-hypertension associations were nonlinear (all P. This study demonstrated an inverse and nonlinear association between dietary polyphenol, especially lignan and stilbene, and hypertension risk. The findings provide implications for hypertension prevention.

Topics: China; Cohort Studies; Diet; Eating; Flavonoids; Humans; Hypertension; Lignans; Polyphenols

Cardiovascular diseases have consistently been the leading cause of death in the United States over the last two decades, with 30% of the adult American population having hypertension. The metabolites of arachidonic acid (AA) in the kidney play an important role in blood pressure regulation. The present study investigates the antihypertensive effect of honokiol (HON), a naturally occurring polyphenol, and examines its correlation to the modulation of AA metabolism.. Spontaneously hypertensive rats (SHR) were randomly divided into four groups. Treatment groups were administered HON intraperitoneally at concentrations of 5, 20, and 50 mg/kg. Blood pressure was monitored at seven-day intervals. After a total of 3 weeks of treatment, the rats were euthanized and the kidney tissues were collected to examine the activity of the two major enzymes involved in AA metabolism in the kidney, namely cytochrome P450 (CYP)4A and soluble epoxide hydrolase (sEH).. Rats treated with HON did not experience the rise in blood pressure observed in the untreated SHR. High-dose HON significantly reduced blood pressure and inhibited the activity and protein expression of the CYP4A enzyme in the rat kidney. The activity of the sEH enzyme in renal cytosol was significantly inhibited by medium and high doses of HON.. Our data demonstrate the antihypertensive effect of HON and provide a novel mechanism for its underlying cardioprotective properties.

Topics: Animals; Antihypertensive Agents; Arachidonic Acid; Biphenyl Compounds; Blood Pressure; Cytochrome P-450 CYP4A; Hypertension; Kidney; Lignans; Rats; Rats, Inbred SHR

In order to examine the association between plasma phytoestrogen concentration (genistein, daidzein, equol and enterolactone) and hypertension, we conducted a nested case-control study for 229 hypertension cases including 112 prehypertension and 159 healthy controls derived from the Korean Multi-center Cancer Cohort (KMCC). The concentration of plasma phytoestrogens was measured using time-resolved fluoroimmunoassay. We assessed the association between plasma phytoestrogens and hypertension using logistic regression models using odds ratio (OR) and 95% confidence interval (95%CI). The highest tertile of plasma equol and enterolactone concentration exhibited a significantly decreased risk of hypertension (equol, OR = 0.34, 95%CI 0.20-0.57; enterolactone, OR = 0.32, 95%CI 0.18-0.57), compared with the lowest tertile. Equol and enterolactone showed reduced ORs for prehypertension (the highest tertile relative to the lowest tertile, OR = 0.50, 95%CI 0.26-0.96; OR = 0.38, 95%CI 0.19-0.75, respectively) and hypertension (OR = 0.42, 95%CI 0.22-0.81; OR = 0.28, 95%CI 0.14-0.54, respectively). There was a stronger association in hypertension (the highest tertile relative to the lowest tertile in obesity vs. non-obesity; equol, OR = 0.06 vs. 0.63; enterolactone, OR = 0.07 vs. 0.46; both

Topics: 4-Butyrolactone; Asian People; Biomarkers; Case-Control Studies; Cohort Studies; Equol; Female; Humans; Hypertension; Lignans; Logistic Models; Male; Phytoestrogens; Republic of Korea; Risk

Flaxseed contains alpha-linolenic acid (ALA), lignans, and dietary fiber, and its intake lowers blood pressure in hypertensive patients. Here, we examined the effects of flaxseed powder, which includes all flaxseed components, flaxseed oil, composed mainly of ALA, flaxseed lignan, and flaxseed fiber, on hypertension and renal damage induced by deoxycorticosterone acetate (DOCA)-salt. Then, we investigated the mechanisms of action associated with the effects of flaxseed.. Flaxseed powder, oil, lignan, or fiber was administered to DOCA-salt rats. Systolic blood pressure (SBP), urinary protein excretion, renal angiotensin converting enzyme (ACE) activity, sympathetic nerve activity, and gene expression of inflammatory mediators in the kidney and hypothalamus were measured.. Flaxseed powder and oil reduced the increases in SBP and urinary protein excretion induced by DOCA-salt treatment, whereas lignan and fiber had no effects. Flaxseed oil suppressed the increase in renal ACE activity, sympathetic nerve activity, and gene expression of renal and hypothalamic inflammatory mediators.. Flaxseed has antihypertensive and renoprotective effects in DOCA-salt rats. These effects are likely principally exerted by ALA. Furthermore, the suppression of renal ACE activity, sympathetic nerve activity, and inflammation is partly involved in the effects of flaxseed.

Topics: Animals; Antihypertensive Agents; Cytokines; Desoxycorticosterone Acetate; Dietary Fiber; Flax; Gene Expression Regulation; Hypertension; Kidney; Lignans; Linseed Oil; Male; Peptidyl-Dipeptidase A; Powders; Protective Agents; Rats, Wistar; Sympathetic Nervous System

Hypertension and endothelial dysfunction are associated with various cardiovascular diseases. Hydrogen sulphide (H

Topics: Acetylation; Angiotensin II; Animals; Aorta; Biphenyl Compounds; Cystathionine gamma-Lyase; Endothelial Cells; HEK293 Cells; Histone Deacetylase 6; Humans; Hydrogen Sulfide; Hypertension; Lignans; Male; Mice; Mice, Inbred C57BL; Proteasome Endopeptidase Complex; Protein Processing, Post-Translational; Proteolysis; Recombinant Proteins

Dietary polyphenols, including phytoestrogens are abundantly present in a balanced diet. Evidence for their role in preventing non-communicable diseases is emerging.. We examined the association between estimated habitual intakes of dietary phytoestrogens and hypertension in a cohort study. The baseline data included 1936 men and women aged 18 years and older. Intakes of total phytoestrogens, isoflavones, and lignans were calculated from validated food frequency questionnaire. Data on the polyphenols content in foods were retrieved from the Phenol-Explorer database.. Individuals in the highest quartile of dietary phytoestrogens intake were less likely to be hypertensive (OR: 0.66, 95% CI: 0.44-0.98); moreover, the association showed a significant decreasing trend. Isoflavones and lignans were not associated with lower odds of hypertension; however, some individual compounds, such as biochanin A and pinoresinol showed an independent inverse association with hypertension.. Dietary phytoestrogens are associated with lower likelihood of hypertension in adults living in the Mediterranean area. Future studies are needed to confirm the present findings (i.e., prospective cohort studies) and to better understand the mechanisms underlying such associations.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Cohort Studies; Energy Intake; Genistein; Humans; Hypertension; Isoflavones; Lignans; Male; Mediterranean Region; Middle Aged; Phytochemicals; Phytoestrogens; Polyphenols; Risk Assessment; Young Adult

The study objectives were to examine total and individual lignan intakes and their dietary sources in postmenopausal Polish women and to investigate the relationship between lignan intake and the prevalence of cardiovascular disease (CVD), hypertension, hypercholesterolemia and central obesity. A total of 2599 postmenopausal women, participants of the Multi-centre National Population Health Examination Surveys (WOBASZ and WOBASZ II) were selected. Of them, 916 had a history of CVD. Nutritional data were collected using a single 24-h dietary recall. Data on lignan content in food, i.e., lariciresinol (LARI), matairesinol (MAT), pinoresinol (PINO) and secoisolariciresinol (SECO), were collected from the available lignan databases. In postmenopausal women, total and individual lignan intakes (SECO, PINO, MAT) were not associated with the prevalence of CVD and its risk factors. The intake of LARI was linked by 30% to the reduced odds for hypercholestrolemia. This study reinforces the existing concept that dietary total lignans are not associated with the prevalence of CVD, and provides further evidence that they are not linked to CVD risk factors such as hypertension, hypercholesterolemia and central obesity. However, the intake of LARI should be taken into consideration in further studies with regard to its potentially beneficial effect in hypercholesterolemia.

Topics: Age Factors; Aged; Cardiovascular Diseases; Cross-Sectional Studies; Diet; Diet Surveys; Female; Humans; Hypercholesterolemia; Hypertension; Lignans; Logistic Models; Middle Aged; Obesity, Abdominal; Odds Ratio; Poland; Postmenopause; Prevalence; Protective Factors; Risk Factors; Sex Factors

Hypertension is one of the most important risk factors in cardiovascular disease and is the most common chronic disease. Mineralocorticoid receptor (MR) antagonists have been successfully used in clinic for the treatment of hypertension.. Our study aims to investigate whether Arctigenin can antagonize MR and inhibit the transcription of Na/K-ATPase.. The yeast two-hybrid assay was used to screen natural products and Arctigenin was identified as an MR antagonist. The direct binding of Arctigenin to MR was determined using assays based on surface plasmon resonance, differential scanning calorimetry and fluorescence quenching. Furthermore, results from mammalian one-hybrid and transcriptional activation experiments also confirmed that Arctigenin can potently antagonize MR in cells. We demonstrated that Arctigenin can decrease the level of Na/K-ATPase mRNA by antagonizing MR in HK-2 cells.. Our findings show that Arctigenin can effectively decrease Na/K-ATPase transcription; thus highlight its potential as an anti-hypertensive drug lead compound.. Our current findings demonstrate that Arctigenin is an antagonist of MR and effectively decreases the Na/K-ATPase 1 gene expression. Our work provides a hint for the drug discovery against cardiovascular disease.

Topics: Animals; Furans; Gene Expression Regulation; HEK293 Cells; Humans; Hypertension; Lignans; Mineralocorticoid Receptor Antagonists; Receptors, Mineralocorticoid; RNA, Messenger; Sodium-Potassium-Exchanging ATPase; Surface Plasmon Resonance; Transcriptional Activation

Fargesin, a bioactive neolignan isolated from magnolia plants, is widely used in the treatment of managing rhinitis, inflammation, histamine, sinusitis, and headache. To provide more biological information about fargesin, we investigated the effects of fargesin on rat aortic rings and 2-kidney, 1-clip (2K1C) hypertensive rats. In vitro, fargesin caused concentration-dependent vasorelaxation in rat isolated aortic rings induced by KCl and norepinephrine. The effect was weakened by endothelium denudation and nitric oxide (NO) synthesis inhibition. In vivo, the evolution of systolic blood pressure (SBP) was followed by weekly measurements. Angiotensin II (Ang II) and endothelin (ET) levels, NO and nitric oxide synthase (NOS), and plasma and liver oxidative stress markers were determined at the end of the experimental period. After 5 weeks of fargesin treatment, we found that fargesin treatment reduced SBP, cardiac hypertrophy, and Ang II and ET levels of hypertensive rats. Increased NOS activity and NO level were observed in fargesin-treated rats. Normalisation of plasma MDA concentrations and improvement of the antioxidant defence system in plasma and liver accompanied the antihypertensive effect of fargesin. Taken together, these results provided substantial evidences that fargesin has antihypertensive effect in 2K1C hypertensive rats via inhibiting oxidative stress and promoting NO release.

Topics: Animals; Antihypertensive Agents; Aorta, Thoracic; Benzodioxoles; Blood Pressure; Hypertension; Lignans; Male; Nitric Oxide; Organ Culture Techniques; Oxidative Stress; Rats; Rats, Wistar; Vasodilation

Gomisin J (GJ) is a small molecular weight lignan found in Schisandra chinensis and has been demonstrated to have vasodilatory activity. In this study, the authors investigated the effect of GJ on blood pressure (BP) in angiotensin II (Ang II)-induced hypertensive mice. In addition, we determined the relative potencies of gomisin A (GA) and GJ with respect to vasodilatory activity and antihypertensive effects. C57/BL6 mice infused s.c. with Ang II (2 μg kg(-1) min(-1) for 2 weeks) showed an increase in BP and a decrease in plasma nitric oxide (NO) metabolites. In the thoracic aortas of Ang II-induced hypertensive mice, a decrease in vascular NO was accompanied by an increase in reactive oxygen species (ROS) production. Furthermore, these alterations in BP, plasma concentrations of NO metabolites and in the vascular productions of NO and ROS in Ang II-treated mice were reversed by the co-administration of GJ (1 and 3 μg kg(-1) min(-1)). In in vitro studies, Ang II decreased the cellular concentration of NO, which was accompanied by a reduction in phosphorylated endothelial nitric oxide synthase (eNOS) and an increase in ROS production. These eNOS phosphorylation and ROS production changes in Ang II-treated cells were also reversed by GJ pretreatment (0-3 μg ml(-1)). Interestingly, the vasodilatory and antihypertensive effects of GJ were more prominent than those of GA. Collectively, an increase in BP in mice treated with Ang II was markedly attenuated by GJ, which was attributed to the preservations of vascular NO bioavailability and eNOS function, and to the inhibition of ROS production in Ang II-induced hypertensive mice.

Topics: Angiotensin II; Animals; Antihypertensive Agents; Biological Availability; Blood Pressure; Cyclooctanes; Dioxoles; Disease Models, Animal; Hypertension; Lignans; Male; Mice; Mice, Inbred C57BL; Nitric Oxide; Nitric Oxide Synthase Type III; Plant Extracts; Polycyclic Compounds; Reactive Oxygen Species; Schisandra; Treatment Outcome; Vasodilator Agents

Patients with prehypertension are more likely to progress to manifest hypertension than those with optimal or normal blood pressure. However, the mechanisms underlying the development from prehypertension to hypertension still remain largely elusive and the drugs for antihypertensive treatment in prehypertension are absent. Here we determined the effects of magnolol (MAG) on blood pressure and aortic vasodilatation to insulin, and investigated the underlying mechanisms. Four-week-old male spontaneous hypertensive rats (SHR) and age-matched normotensive Wistar-Kyoto (WKY) control rats were used. Our results shown that treatment of young SHRs with MAG (100 mg/kg/day, o.g.) for 3 weeks decreased blood pressure, improved insulin-induced aorta vasodilation, restored Akt and eNOS activation stimulated by insulin, and increased PPARγ and decreased TRB3 expressions. In cultured human umbilical vein endothelial cells (HUVECs), MAG incubation increased PPARγ, decreased TRB3 expressions, and restored insulin-induced phosphorylated Akt and eNOS levels and NO production, which was blocked by both PPARγ antagonist and siRNA targeting PPARγ. Improved insulin signaling in HUVECs by MAG was abolished by upregulating TRB3 expression. In conclusion, treatment of young SHRs with MAG beginning at the prehypertensive stage decreases blood pressure via improving vascular insulin resistance that is at least partly attributable to upregulated PPARγ, downregulated TRB3 and consequently increased Akt and eNOS activations in blood vessels in SHRs.

Topics: Animals; Aorta; Biphenyl Compounds; Blood Pressure; Blood Vessels; Densitometry; Human Umbilical Vein Endothelial Cells; Humans; Hypertension; Insulin; Insulin Resistance; Lignans; Nitric Oxide Synthase Type III; PPAR gamma; Protein Serine-Threonine Kinases; Proto-Oncogene Proteins c-akt; Rats, Inbred SHR; Rats, Inbred WKY; Signal Transduction; Up-Regulation; Vasodilation

The blood pressure lowering effect of sesamin has been demonstrated to be associated with the increase in vascular nitric oxide (NO) biological activity by our previous studies and others. The present study was designed to explore the underlying mechanisms involved in the effect of sesamin on aortic NO bioactivity in spontaneously hypertensive rats (SHRs).. Sesamin was orally administered for 8 consecutive weeks in SHRs. Systolic blood pressure (SBP) was measured using the tail-cuff method. The aortas were isolated and in vitro vascular reactivity studies were performed. Superoxide anion production in carotid arteries was assessed by dihydroethidium fluorescence staining. The protein expression of endothelial nitric oxide synthase (eNOS), phosphorylated eNOS (P-eNOS), dihydrofolate reductase (DHFR), nicotinamide adenine dinucleotide phosphate oxidase subunit p47phox, and copper, zinc superoxide dismutase (Cu/Zn-SOD) in aortas was detected by Western blotting. The dimeric form of eNOS in aortas was determined by low-temperature sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Aortic level of nitrotyrosine and activities of antioxidant enzymes, namely, total SOD (T-SOD), glutathione peroxidase (GPx) and catalase were also detected.. In SHRs, sesamin treatment reduced SBP, improved vascular relaxation induced by acetylcholine and enhanced aortic NO bioactivity. Sesamin treatment enhanced NO biosynthesis in SHR aortas was due to upregulated P-eNOS and suppressed eNOS uncoupling, and the latter effect might be attributed to decreased nitrotyrosine and upregulated DHFR. Sesamin also reduced the NO oxidative inactivation and decreased the superoxide anion production through downregulation of p47(phox) and amelioration of eNOS uncoupling. In addition, sesamin treatment did not alter the levels of GPx and catalase activity but obviously reduced the compensatory elevated T-SOD activity and Cu/Zn-SOD protein expression.. Chronic treatment with sesamin could reduce hypertension and improve endothelial dysfunction through enhancement of NO bioactivity in SHR aortas.

Topics: Animals; Antihypertensive Agents; Antioxidants; Aorta; Blood Pressure; Blotting, Western; Dioxoles; Down-Regulation; Electrophoresis, Polyacrylamide Gel; Endothelium, Vascular; Hypertension; Lignans; Male; Nitric Oxide; Nitric Oxide Synthase Type III; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Superoxide Dismutase; Up-Regulation

To study the protective effect of Arctigenin in goto-kakizaki (GK) rats combined with hypertension macroangiopathy. Six-week-old GK rats were divided randomly according to blood glucose level into four groups: the model group and low, middle and high dose arctigenin groups (12.5, 25, 50 mg x kg(-1)), with Wistar rats as the normal group. All of GK rats were given high-glucose and high-fat diet. After 16 weeks, GK rats were orally administrated with 10 mg x kg(-1) x d(-1) N-Ω-nitro-L-arginine methyl ester for eight weeks. During the modeling, all of arctigenin groups were orally administrated with different dose of arctigenin twice a day; The model group and the normal group were given solvents. At the beginning, mid-term and end of the experiment, blood glucose was measured. At the end of the experiment, efforts were made to detect blood pressure, collect abdominal aortic blood after anesthesia, fix thoracic aorta after bloodletting to make paraffin sections, observe morphological characteristics and detect the expression of VEGF by immunohistochemistry. According to the results, the blood glucose rose in all GK rats, with no significant difference between the drug group and the model group. At the end of the experiment, the blood pressure significantly increased in GK rats, indicating that Arctigenin could notably reduce the blood pressure in GK rats in a dose-dependent manner. The blood routine test showed increases in both the total white blood cell count and differential blood count, MPV and PDW, abnormal blood platelet parameters and decrease in PLT in GK rats, suggesting that Arctigenin could remarkably reduce the total white blood cell count and differential blood count, MPV and PDW. The thoracic aortic morphological observation revealed obvious endangium lesions in GK rats, demonstrating that Arctigenin could ameliorate the lesion extent. VEGF immumohistochemical staining showed a higher VEGF expression in the model group but lower expression in Arctigenin groups. In conclusion, Arctigenin had a protective effect on aorta in GK rats. Its mechanism may be related to blood pressure lowering, anti-inflammation, improvement in blood platelet function and reduction of VEGF expression.

Topics: Animals; Blood Glucose; Blood Pressure; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Disease Models, Animal; Drugs, Chinese Herbal; Furans; Humans; Hypertension; Lignans; Male; Rats; Rats, Wistar

Arctigenin is a bioactive constituent from dried seeds of Arctium lappa L., which was traditionally used as medicine. Arctigenin exhibits various bioactivities, but its effects on blood pressure regulation are still not widely studied. In this study, we investigated antihypertensive effects of arctigenin by long-term treatment in spontaneously hypertensive rats (SHRs). Arctigenin (50 mg/kg) or vehicle was administered to SHRs or Wistar rats as negative control by oral gavage once a day for total 8 weeks. Nifedipine (3 mg/kg) was used as a positive drug control. After treatment, hemodynamic and physical parameters, vascular reactivity in aorta, the concentration of plasma arctigenin and serum thromboxane B2, NO release and vascular p-eNOS, p-Akt, caveolin-1 protein expression, and vascular superoxide anion generation and p47phox protein expression were detected and analyzed. The results showed that arctigenin significantly reduced systolic blood pressure and ameliorated endothelial dysfunction of SHRs. Arctigenin reduced the levels of thromboxane B2 in plasma and superoxide anion in thoracic aorta of SHRs. Furthermore, arctigenin increased the NO production by enhancing the phosphorylation of Akt and eNOS (Ser 1177), and inhibiting the expression of NADPH oxidase in thoracic aorta of SHRs. Our data suggested that antihypertensive mechanisms of arctigenin were associated with enhanced eNOS phosphorylation and decreased NADPH oxidase-mediated superoxide anion generation.

Topics: Animals; Antihypertensive Agents; Blood Pressure; Dose-Response Relationship, Drug; Furans; Gene Expression Regulation, Enzymologic; Hypertension; Lignans; Male; NADPH Oxidases; Nitric Oxide Synthase; Rats; Rats, Inbred SHR; Rats, Sprague-Dawley

In this study, we investigated the antihypertensive effects of Acanthopanax divaricatus var. chiisanensis extract (AE) and its active compound, acanthoside D (AD), on arterial blood pressure (BP) in vivo and endothelial function in vitro. We hypothesized that AE has antihypertensive effects, which is attributed to enhancement of endothelial function via the improvement of nitric oxide synthesis or the angiotensin II (Ang II) response. Spontaneously hypertensive rats (SHRs) and Wistar-Kyoto rats (WKYs) were randomly divided into 7 groups and then fed the following diets for 14 weeks: WKY fed a normal diet (WN); SHR fed a normal diet (SN); SHR fed a high-cholesterol (HC) diet (SH); SHR fed a HC diet with AE of 150, 300, 600 mg/kg body weight (SH-L, SH-M, SH-H); and SHR fed an HC diet with AD of 600 μg/kg body weight (SH-D). Blood pressure was significantly reduced in the SH-H compared with the SH from week 10 until week 14; BP was also significantly decreased in the SHR fed a HC diet with AE of 300 at week 14. Aortic wall thickness showed a tendency to decrease by AE and AD treatment. The SH-H showed increased endothelial nitric oxide synthase (eNOS) expression in the intima and media, compared with the SH. Furthermore, a significant increase in intracellular nitric oxide production was induced by AE and AD treatment in human umbilical vein endothelial cells. A significant increase of phospho-eNOS was found with a high dose of AE in human umbilical vein endothelial cells but not with AD. These results suggest that AE can regulate BP and improve endothelial function via eNOS-dependent vasodilation.

Topics: Animals; Antihypertensive Agents; Aorta; Blood Pressure; Eleutherococcus; Endothelium, Vascular; Furans; Glucosides; Humans; Hypertension; Lignans; Male; Nitric Oxide; Nitric Oxide Synthase; Phytotherapy; Plant Extracts; Rats, Inbred SHR; Rats, Inbred WKY; Signal Transduction; Umbilical Veins; Vasodilation

Sesamin is one of the major lignans in sesame seeds with antihyperlipidemic, antioxidative and antihypertensive activities. The aim of this study was to examine the effects of sesamin on arterial function in spontaneously hypertensive rats (SHRs).. SHRs were orally administered sesamin (40, 80 and 160 mg·kg(-1)·d(-1)) for 16 weeks. After the rats were killed, thoracic aortas were dissected out. The vasorelaxation responses of aortic rings to ACh and nitroprusside were measured. The expression of eNOS and NADPH oxidase subunits p47(phox) and p22(phox) in aortas were detected using Western blotting and immunohistochemistry. Aortic nitrotyrosine was measured with ELISA. The total antioxidant capacity (T-AOC) and MDA levels in aortas were also determined.. The aortic rings of SHRs showed significantly smaller ACh-induced and nitroprusside-induced relaxation than those of control rats. Treatment of SHRs with sesamin increased both the endothelium-dependent and endothelium-independent relaxation of aortic rings in a dose-dependent manner. In aortas of SHRs, the level of T-AOC and the expression of nitrotyrosine, p22(phox) and p47(phox) proteins were markedly increased, while the level of MDA and the expression of eNOS protein were significantly decreased. Treatment of SHRs with sesamin dose-dependently reversed these biochemical and molecular abnormalities in aortas.. Long-term treatment with sesamin improves arterial function in SHR through the upregulation of eNOS expression and downregulation of p22(phox) and p47(phox) expression.

Topics: Animals; Aorta, Thoracic; Dioxoles; Down-Regulation; Hypertension; Lignans; Male; NADPH Oxidases; Nitric Oxide Synthase Type III; Organ Culture Techniques; Protein Subunits; Random Allocation; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Up-Regulation

This study was designed to evaluate the in vivo cardioprotective effects of food-derived sesamin in spontaneously hypertensive rats (SHR). The study was performed with 17-week-old male normotensive Wistar-Kyoto rats (WKY) and SHR which are untreated or treated with orally administered sesamin for 16 weeks before they were sacrificed. Long-term treatment with sesamin obviously improved left ventricular (LV) hypertrophy and fibrosis in SHR, as indicated by the decrease of LV weight/body weight, myocardial cell size, cardiac fibrosis and collagen type I expression as well as the amelioration of the LV ultrastructure. These effects were associated with reduced systolic blood pressure, enhanced cardiac total antioxidant capability and decreased malondialdehyde content, nitrotyrosine level and transforming growth factor β1 (TGF-β1) expression. All these results suggest that chronic treatment with sesamin improves LV remodeling in SHR through alleviation of oxidative and nitrative stress, reduction of blood pressure and downregulation of TGF-β1 expression.

Topics: Animals; Antihypertensive Agents; Blood Pressure; Collagen Type I; Dioxoles; Disease Models, Animal; Down-Regulation; Fibrosis; Heart; Hypertension; Hypertrophy, Left Ventricular; Lignans; Male; Malondialdehyde; Myocytes, Cardiac; Rats; Rats, Inbred SHR; Rats, Inbred WKY; RNA, Messenger; Transforming Growth Factor beta1; Tyrosine; Ventricular Remodeling

To investigate the protective effects and the underlying mechanism of Eucommia lignans against hypertensive renal injury.. Ten-week-old Wistar Kyoto rats and age matched spontaneously hypertension rats were used in the study. The SHR were randomly divided into 4 groups (n=7 for each group) and received different treatment for 16 weeks, which including saline, Captopril, Epalrestat and Eucommia lignans, respectively. System blood pressures of the rats were monitored once every 4 weeks. N-Acetyl-β-D-glucosaminidase (NAG) activity and the ratio of albumin and urinary creatinine were chosen as the indices of kidney function. Then the structure and renal collagen type III expression of glomerular basement membrane were observed by microscopy and the renal aldose reductase (AR) expression was measured by immunohistochemistry. In vitro, the proliferation of mesangial cells induced by AngII was assayed by MTT, and the mRNA expression of AR was measured by RT-real-time PCR.. The renal function, evaluated by NAG enzyme activity and the ratio of albumin to urinary creatinine, was significantly ameliorated by Eucommia lignans treatment. Meanwhile, Eucommia lignans decreased both the protein (P<0.05) and the mRNA expressed lever of AR (P<0.05). Eucommia lignans also decreased the high expression of collagen type III in SHR (P<0.05) and inhibited the proliferation of renal mesangial cells induced by AngII (P<0.05).. Eucommia lignans have protective effects against hypertensive renal injury, and the protective effects may be partly due to inhibition of aldose reductase.

Topics: Acetylglucosaminidase; Albuminuria; Aldehyde Reductase; Animals; Antihypertensive Agents; Biomarkers; Blood Pressure; Cell Proliferation; Cells, Cultured; Collagen Type III; Creatinine; Disease Models, Animal; Down-Regulation; Enzyme Inhibitors; Eucommiaceae; Glomerular Basement Membrane; Hypertension; Immunohistochemistry; Kidney; Kidney Diseases; Lignans; Male; Plant Extracts; Plants, Medicinal; Rats; Rats, Inbred SHR; Rats, Inbred WKY; RNA, Messenger; Time Factors

Gomisin A (GA) is a small molecular weight lignan present in Schisandra chinensis, and has been demonstrated to have vasodilatory activity. In the present study, we investigated the effect of GA on blood pressure (BP) in angiotensin II (Ang II)-induced hypertensive mice. C57/BL6 mice infused subcutaneously with Ang II (1 and 2 μg kg⁻¹ per min for 2 weeks) showed an increase in BP with a decrease in nitric oxide (NO) metabolites in plasma, and a negative correlation between these two parameters was demonstrated. In the thoracic aorta from Ang II-induced hypertensive mice, a decrease in vascular NO that was accompanied by a diminution of phosphorylated endothelial nitric oxide synthase (eNOS), as well as by increased reactive oxygen species (ROS) production, was demonstrated. These alterations in BP, eNOS phosphorylation and ROS production in the vasculature of Ang II-treated mice were markedly and dose-dependently reversed by simultaneous administration of GA (2 and 10 μg kg⁻¹ per min). In addition, Ang II-induced ROS production in cultured vascular cells such as endothelial cells and vascular smooth muscle cells was markedly attenuated by GA. These results suggested that GA attenuated the increase in BP via preservation of vascular NO bioavailability not only by inhibiting ROS production but also by preventing the impairment of eNOS function in the vasculature of Ang II-induced hypertensive mice.

Topics: Angiotensin II; Animals; Antihypertensive Agents; Blood Pressure; Blood Vessels; Cells, Cultured; Cyclooctanes; Dioxoles; Dose-Response Relationship, Drug; Hypertension; Lignans; Male; Mice; Mice, Inbred C57BL; Nitric Oxide; Nitric Oxide Synthase Type III; Phosphorylation; Reactive Oxygen Species; Schisandra; Vasoconstrictor Agents

Topics: Angiotensin II; Animals; Antihypertensive Agents; Cyclooctanes; Dioxoles; Hypertension; Lignans; Male; Nitric Oxide; Schisandra; Vasoconstrictor Agents

To investigate the effects of lignans extracted from Eucommia ulmoides and epalrestat on vascular remodeling in spontaneously hypertensive rats.. Ten-week-old male spontaneously hypertensive rats were randomly divided into 3 groups (12 rats each group), and treated orally with 100 mg/kg/d of captopril (an angiotensin-converting enzyme inhibitor), 100 mg/kg/d of epalrestat (an aldose reductase inhibitor) and 300 mg/kg/d of lignans by gavage daily for 16 weeks, respectively. Sex-, age-, and number-matched spontaneously hypertensive rats and normotensive Wistar Kyoto rats, were treated with distilled water (vehicle) as controls. The rats were weighed weekly. Mean arterial blood pressure and heart rate were measured periodically by non-invasive blood pressure monitoring. They were sacrificed at the end of experiment (26-week-old). Superior mesenteric artery and aorta were isolated for determination of histomorphometry and the expression of aldose reductase by immunohistochemistry.. Captopril and lignans, but not epalrestat, decreased mean arterial blood pressure in spontaneously hypertensive rats. Vascular remodeling was improved in all three treated groups by histomorphometry.. Both lignans and epalrestat reversed hypertensive vascular remodeling. Aldose reductase played a vital role in the pathologic process of hypertensive vascular remodeling rather than elevation of blood pressure. These data suggested that aldose reductase could be a new therapeutic target for the treatment of cardiovascular diseases.

Topics: Aldehyde Reductase; Animals; Aorta; Blood Pressure; Captopril; Drugs, Chinese Herbal; Enzyme Inhibitors; Eucommiaceae; Female; Heart Rate; Hypertension; Lignans; Male; Mesenteric Artery, Superior; Plant Bark; Random Allocation; Rats; Rats, Inbred SHR; Rats, Wistar; Rhodanine; Thiazolidines

To evaluate the effects of Tiangou Jiangya capsule on blood pressure and hemodynamics in anesthetized Beagle dogs.. Anesthetized dogs were divided into five groups: Tiangou Jiangya capsule 3-dose groups as 1.6, 3.2, 6.4 g x kg(-1), positive control group was giving captopril, negative control was giving 0.5% CMC-Na, duodenal administration. The blood pressure and hemodynamic changes were observed.. The systolic blood pressure of middle-dose Tiangou Jiangya capsule group was significantly reduced at 30 min after administration. The systolic blood pressure (SAP) and diastolic blood pressure (DAP) of high-dose group of Tiangou Jiangya capsule was significantly reduced at 15 min to 90 min after administration. High-dose Tiangou Jiangya capsule can also significantly reduce cardiac work (LVW) and total peripheral resistance (TPR). Tiangou Jiangya capsule had no significant effect on the other hemodynamic parameters and myocardial oxygen consumption.. Tiangou Jiangya capsule has a significant effect on reducing blood pressure, which is related to the reducing total peripheral resistance and reducing cardiac work. The result can provide a reference to further clarify the Tiangou Jiangya capsule mechanism on reducing blood pressure.

Topics: Animals; Antihypertensive Agents; Benzyl Alcohols; Blood Pressure; Disease Models, Animal; Dogs; Drugs, Chinese Herbal; Female; Flavonoids; Furans; Glucosides; Heart Rate; Hemodynamics; Hypertension; Lignans; Male; Oxygen Consumption; Vascular Resistance

To investigate the effects of Tiangou Jiangya capsule on blood pressure of spontaneous hypertensive rats.. The 13-14 week SPF rats were selected and randomly divided into model groups, the low, middle, high dose of Tiangou Jiangya capsule groups, positive control group administrated with captopril. Drugs were intragastric administrated once per day, lasting four weeks. The blood pressure, heart rate, heart ventricle indexes, urinary volume and the level of PRA,angiotensing II (Ang II), aldosterone (ALD) of rats were observed.. The low, middle, high dose of Tiangou Jiangya capsule can remarkably reduce the systolic pressure, diastolic pressure and mean arterial pressure of spontaneous hypertensive rats (P < 0.05 or P < 0.01). The low, middle dose can reduce the heart rate of rats (P < 0.01). The low dose can effectively inhibit the left ventricle indexes (P < 0.05). The Tiangou Jiangya capsule has no markedly effects on the renin-angiotensin-aldosterone system (RAAS) activity and urinary output of rats.. The results indicate that the Tiangou Jiangya capsule has evident effect of lowering blood pressure of rats, which is related to reducing heart rate, heart ventricle indexes, and has no effect on the RAAS and diuresis.

Topics: Animals; Antihypertensive Agents; Benzyl Alcohols; Blood Pressure; Disease Models, Animal; Diuresis; Drugs, Chinese Herbal; Flavonoids; Furans; Glucosides; Heart Rate; Hypertension; Lignans; Male; Rats; Rats, Inbred SHR; Renin-Angiotensin System; Ventricular Function, Left

The present study was performed to evaluate the antihypertensive effects of honokiol in vivo in spontaneously hypertensive rats (SHR). The effects of honokiol were investigated by determination of the blood pressure, vascular reactivity, oxidative parameters, and histologic change in the aorta. Long-term administration of honokiol (400 mg/kg/d) to SHR decreased systolic blood pressure significantly. Honokiol (200, 400 mg/kg/d) enhanced the aortic relaxation in response to acetylcholine after 49-d treatment, but had no significant effects on the relaxation to sodium nitroprusside. The oral administration of honokiol significantly increased the plasma level of NO(2(-))/NO(3(-)), but decreased the level of malondialdehyde in liver of SHR compared with the control vehicle. In addition, SHR administered honokiol showed significant reductions in the elastin bands and media thickness in the aorta. These results suggest that chronic treatment with honokiol exerts an antihypertensive effect in SHR, and its vasorelaxant action and antioxidant properties may contribute to reducing the elevated blood pressure.

Topics: Acetylcholine; Animals; Antihypertensive Agents; Antioxidants; Aorta; Biphenyl Compounds; Blood Pressure; Elastin; Hypertension; Lignans; Liver; Magnolia; Malondialdehyde; Nitrates; Nitrites; Nitroprusside; Plant Extracts; Rats; Rats, Inbred SHR; Vasodilator Agents

1. Dietary sesamin, a sesame lignan, is known to suppress the development of experimental hypertension in rats partly through its inhibitory effect on vascular O(2)(-) production. Therefore, in the present study, we examined whether sesamin feeding had any effect on vascular NADPH oxidase using aortas from deoxycorticosterone acetate (DOCA) salt hypertensive rats. 2. After a 5 week feeding and treatment period, aortic O(2)(-) production and NADPH oxidase activity were measured using the lucigenin assay. Reverse transcription-polymerase chain reaction was performed to analyse aortic expression of NADPH oxidase subunit (p22phox, gp91phox, Nox1 and Nox4) mRNA. 3. Sesamin feeding markedly suppressed DOCA salt-induced hypertension and significantly decreased aortic O(2)(-) production. DOCA salt treatment increased NADPH oxidase activity and elevated aortic mRNA expression of p22phox, gp91phox, Nox1 and Nox4. Sesamin feeding abolished the increase in NADPH oxidase activity and, furthermore, significantly suppressed increases in p22phox, gp91phox and Nox1 mRNA expression. 4. In conclusion, dietary sesamin prevented DOCA salt-induced increases in NADPH oxidase activity and subunit mRNA expression. These effects seem to be involved in the anti-oxidant and antihypertensive effects of sesamin.

Topics: Animals; Aorta; Cyclic N-Oxides; Desoxycorticosterone; Dietary Supplements; Dioxoles; Hypertension; Lignans; Male; NADPH Oxidases; Rats; Rats, Sprague-Dawley; Spin Labels

Sesamin, a major lignan in sesame seeds and oil, has been known to lower blood pressure in several types of experimental hypertensive animals. A recent study demonstrated that sesamin metabolites had in vitro radical-scavenging activities. Thus, we determined whether the antioxidative effect of sesamin metabolites modulate the vascular tone and contribute to the in vivo antihypertensive effect of sesamin. We used four demethylated sesamin metabolites: SC-1m (piperitol), SC-1 (demethylpiperitol), SC-2m [(1R,2S,5R,6S)-6-(4-hydroxy-3-methoxyphenyl)-2-(3,4-dihydroxyphenyl)-3,7-dioxabicyclo[3,3,0]octane], and SC-2 [(1R,2S,5R, 6S)-2,6-bis(3,4-dihydroxyphenyl)-3,7-dioxabicyclo-[3,3,0]octane]. SC-1, SC-2m, and SC-2, but not SC-1m, exhibited potent radical-scavenging activities against the xanthine/xanthine oxidase-induced superoxide production. On the other hand, SC-1m, SC-1, and SC-2m produced endothelium-dependent vasorelaxation in phenylephrine-precontracted rat aortic rings, whereas SC-2 had no effect. The SC-1m- and SC-1-induced vasorelaxations were markedly attenuated by pretreatment with a nitric oxide synthase (NOS) inhibitor, NG-nitro-L-arginine (NOARG), or a soluble guanylate cyclase inhibitor, 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one. Neither SC-1m nor SC-1 changed the expression level of endothelial NOS protein in aortic tissues. The antihypertensive effects of sesamin feeding were not observed in chronically NOARG-treated rats or in deoxycorticosterone acetate-salt-treated endothelial NOS-deficient mice. These findings suggest that the enhancement of endothelium-dependent vasorelaxation induced by sesamin metabolites is one of the important mechanisms of the in vivo antihypertensive effect of sesamin.

Topics: Animals; Antihypertensive Agents; Antioxidants; Dioxoles; Hypertension; Lignans; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Nitric Oxide; Nitric Oxide Synthase Type III; Protein Binding; Rats; Rats, Sprague-Dawley; Vasodilation

Phytoestrogens have been suggested to lower cardiovascular disease risk, but existing research focused on non-Western high intake levels and on risk factors. We investigated whether habitual low phytoestrogen intake is associated with manifest cardiovascular disease risk.. Between 1993 and 1997, 16,165 women 49 to 70 years old and free from cardiovascular disease were enrolled in the Dutch Prospect-EPIC cohort (European Prospective study Into Cancer and nutrition) and followed up for a median period of 75 months. At enrollment, women filled in questionnaires on chronic disease risk factors and nutrition. Intake of phytoestrogens was estimated using the food frequency questionnaire covering regular dietary intake of 178 food items in the year before enrollment. Cox regression analysis was used to estimate hazard ratios of cardiovascular disease for quartiles of phytoestrogen intake adjusted for age at intake, body mass index, smoking, physical activity, hypertension, hypercholesterolemia, use of hormone replacement therapy, menopausal status, and intake of total energy, total fiber, vegetables, fruit, and alcohol. In total, 372 women experienced a coronary event (CHD) (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9], 410 to 414, 427.5) and 147 women a cerebrovascular event (CVD) (ICD-9, 430 to 438) during follow-up. Overall, neither isoflavones nor lignans were associated with decreased cardiovascular disease risk. When stratifying for ever versus never smokers, CHD risk decreased with increasing lignan intake for ever smokers.. Our results do not support the presence of a protective effect of higher intake of phytoestrogens in low doses on cardiovascular disease risk, although a small risk reduction with higher lignan intake cannot be excluded for smokers.

Topics: Aged; Alcohol Drinking; Body Mass Index; Cardiovascular Diseases; Cohort Studies; Coronary Disease; Dietary Fiber; Energy Intake; Feeding Behavior; Female; Follow-Up Studies; Fruit; Hormone Replacement Therapy; Humans; Hypercholesterolemia; Hypertension; Isoflavones; Lignans; Menopause; Middle Aged; Netherlands; Nutrition Surveys; Phytoestrogens; Proportional Hazards Models; Prospective Studies; Risk; Smoking; Stroke; Surveys and Questionnaires; Vegetables

To observe the effect and mechanism of clausenamide on the expression of Bcl-2 and apoptosis after focal cerebral ischemia/reperfusion in renovascular hypertensive rats.. Seventy-five renovascular hypertensive rats were randomly divided into three groups (25 in each group): clausenamide intervention group, single ischemia/reperfusion model group and sham-operated group. Focal cerebral ischemia was reproduced by ligature for 2 hours and loosening of the ligature in the rats. No arterial ligature was applied in sham-operated group. Computerized pathological image analyzer was used to determine the number of cells positive for Bcl-2 by immunohistochemical staining, and also the counts of apoptotic cells after TdT-mediated dUTP nick end labeling (TUNEL) staining respectively in coronal sections of brain after reperfusion (6, 12, 24, 48 and 72 hours).. (1) The expression of Bcl-2 protein was detected 6 hours after reperfusion, peaking at 24 hours, then declined gradually. The Bcl-2 protein positive cell counts at every time point in clausenamide intervention group were significantly higher than simple ischemia/reperfusion model group (all P<0.01). (2) The number of apoptotic cells was increased with reperfusion, reaching its peak at 72 hours. The apoptosis counts in clausenamide intervention group were significantly lower than single ischemia/reperfusion model group (all P<0.01). At all time points, except at 48 hours after reperfusion, as there was no significant difference (all P>0.05). No Bcl-2 positive cells and only 0-2 apoptotic cells could be discernible in brain sections from sham-operated animals or in the contralateral side of ischemia in animals of the other groups.. Expression of Bcl-2 protein is enhanced and apoptosis appears after focal cerebral ischemia/reperfusion in rat brain. Clausenamide can enhance the expression of Bcl-2 protein and inhibit apoptosis remarkably. Clausenamide may coordinate with Bcl-2 in inhibiting apoptosis. This may be the mechanism of protection of brain cells from ischemic damage of clausenamide treatment.

Topics: Animals; Apoptosis; Brain Ischemia; Disease Models, Animal; Hypertension; Lactams; Lignans; Male; Proto-Oncogene Proteins c-bcl-2; Random Allocation; Rats; Rats, Wistar; Reperfusion Injury

To investigate the effects of low levels of intake of phytoestrogens in Western habitual diet on vascular function.. A cross-sectional study.. A population-based study.. A total of 301 postmenopausal women aged 60-75 years living in The Netherlands. DETERMINANT: Dietary phytoestrogen intake as assessed using a food frequency questionnaire covering the year prior to enrollment.. Blood pressure, hypertension, endothelial function and ankle brachial index.. The median isoflavone intake was 0.2 mg in the lowest tertile and 11.4 mg in the highest tertile. Median lignan intake was 0.8 and 2.2 mg, respectively. No associations were found for higher intake of isoflavones, systolic and diastolic blood pressures, ankle-arm blood pressure index, endothelial function or hypertension. For lignans no association was found for ankle-arm blood pressure index or endothelial function, but we did observe lower systolic and diastolic blood pressures and a lower prevalence of hypertension (systolic blood pressure difference T3-T1, -11.2 mmHg, 95% confidence interval = -17.8 to -4.5, P for trend = 0.001; diastolic blood pressure difference T3-T1, -3.6 mmHg, 95% confidence interval = -7.8 to 0.6, P for trend = 0,08; and prevalence of hypertension, odds ratio T3 versus T1 = 0.41, 95% confidence interval = 0.22-0.76, P for trend over tertiles = 0.004).. The results of this study suggest a protective effect of dietary lignan intake on blood pressure and hypertension, even at low levels.

Topics: Aged; Ankle; Blood Pressure; Brachial Artery; Cross-Sectional Studies; Diet Surveys; Female; Humans; Hypertension; Lignans; Middle Aged; Phytoestrogens; Postmenopause; Prevalence

The preventive effects of sesamin, a lignan from sesame oil and vitamin E on hypertension and thrombosis were examined using stroke-prone spontaneously hypertensive rats (SHRSP). Animals at 5 weeks of age were separated into four groups: (i) control group; (ii) vitamin E group, which was given 1000 mg alpha-tocopherol/kg diet; (iii) sesamin group, given 1000 mg sesamin/kg diet; and (iv) vitamin E plus sesamin group, given 1000 mg alpha-tocopherol plus 1000 mg sesamin/kg diet for 5 weeks from 5 to 10 weeks of age. Resting blood pressure was measured by the tail-cuff method once weekly. A closed cranial window was created in the right parietal bone of the rat and platelet-rich thrombi were induced in vivo using a helium-neon laser technique. The number of laser pulses required for formation of an occlusive thrombus was used as an index of thrombotic tendency. In control rats, systolic blood pressure and the amount of urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) became significantly elevated with age. However, the elevation in blood pressure and 8-OHdG were significantly suppressed in rats administered vitamin E, sesamin, or vitamin E plus sesamin. At 10 weeks, the number of laser pulses required to induce an occlusive thrombus in arterioles of the control group was significantly lower than in the other groups (P < 0.05). These results indicate that chronic ingestion of vitamin E and sesamin attenuated both elevation in blood pressure, oxidative stress and thrombotic tendency, suggesting that these treatments might be beneficial in the prevention of hypertension and stroke.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Antihypertensive Agents; Antioxidants; Blood Pressure; Deoxyguanosine; Dioxoles; Fibrinolytic Agents; Hypertension; Intracranial Thrombosis; Lignans; Rats; Rats, Inbred SHR; Stroke; Vitamin E

In the present study, we evaluated the relationship between the antihypertensive effect of sesamin, a lignan from sesame oil, and its antioxidative activity in deoxycorticosterone acetate (DOCA)-salt hypertensive rats. After a 5-week treatment period, systolic blood pressure was significantly elevated in normal diet-fed DOCA-salt animals compared with cases in sham-operated animals. Sesamin feeding, tempol (a superoxide dismutase mimetic) treatment or antihypertensive drugs combination (triple therapy; reserpine, hydralazine, hydrochlorothiazide) significantly suppressed the development of DOCA-salt-induced hypertension. Compared with sham-operated rats, the normal diet-fed DOCA-salt rats revealed marked increases in aortic superoxide (O(2)(-)) production. These increases in O(2)(-) production were significantly suppressed by sesamin feeding or tempol treatment, but not by triple therapy. Acetylcholine (Ach)-induced endothelium-dependent relaxation was markedly decreased in normal diet-fed DOCA-salt rats, compared with cases in sham-operated rats. Sesamin feeding and triple therapy significantly improved the DOCA-salt-induced impairment of endothelium-dependent relaxation. However, tempol treatment had no effect on the impaired vasodilator responses induced by DOCA-salt treatment. In DOCA-salt rats with or without sesamin feeding, systolic blood pressure significantly correlated with both aortic O(2)(-) production and endothelium-dependent vascular relaxation. These findings suggest that sesamin feeding inhibits the enhancement of aortic O(2)(-) production in DOCA-salt hypertensive rats, and this effect may contribute to the antihypertensive effect of sesamin. Sesamin feeding-induced improvement of endothelial dysfunction seems to result from the above antioxidative and antihypertensive effects.

Topics: Acetylcholine; Administration, Oral; Animals; Antihypertensive Agents; Aorta; Blood Pressure; Cyclic N-Oxides; Desoxycorticosterone; Dioxoles; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Drug Therapy, Combination; Endothelium, Vascular; Hypertension; Hypertension, Renovascular; Lignans; Male; Muscle, Smooth, Vascular; Oxidative Stress; Rats; Rats, Sprague-Dawley; Spin Labels; Superoxides; Vasodilation

We previously demonstrated the preventive effect of sesamin, a lignan from sesame oil, on the development of several experimental models of hypertension. In the present study, we explored the mechanisms underlying the antihypertensive effect of sesamin using the deoxycorticosterone acetate (DOCA)-salt rat hypertensive model. After a 5-week treatment period, aortic superoxide (O2-) production was measured in the lucigenin chemiluminescence assay. Chemiluminescence signals significantly decreased in sesamin-containing diet-fed DOCA-salt hypertensive rats compared with those in the normal diet-fed DOCA-salt rats, although the signals in sham-operated control animals were not affected by the sesamin feeding. In addition, there was a positive correlation between systolic blood pressure and aortic O2- production. These findings suggest that sesamin feeding inhibits enhanced vascular O2- production in DOCA-salt hypertensive rats and that the antioxidative action of sesamin may contribute to its antihypertensive activity.

Topics: Animals; Antihypertensive Agents; Aorta, Thoracic; Dioxoles; Hypertension; Lignans; Male; Rats; Rats, Sprague-Dawley; Superoxides

The preventive effects of sesamin, a lignan from sesame oil, and vitamin E on hypertension and thrombosis were examined using stroke-prone spontaneously hypertensive rats (SHRSP). At 5 weeks of age the animals were separated into four groups: (i) a control group; (ii) a vitamin E group, which was given a 1,000 mg alpha-tocopherol/kg diet; (iii) a sesamin group, given a 1,000 mg sesamin/kg diet; and (iv) a vitamin E plus sesamin group, given a 1,000 mg alpha-tocopherol plus 1,000 mg sesamin/kg diet for 5 weeks from 5 to 10 weeks of age. Resting blood pressure was measured by the tail-cuff method once weekly. A closed cranial window was created and platelet-rich thrombi were induced in vivo using a helium-neon laser technique. The number of laser pulses required for formation of an occlusive thrombus was used as an index of thrombotic tendency. In control rats, systolic blood pressure and the amount of urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) became significantly elevated with age. However, the elevation in blood pressure and 8-OHdG were significantly suppressed in rats administrated vitamin E, sesamin, or vitamin E plus sesamin. At 10 weeks, the number of laser pulses required to induce an occlusive thrombus in arterioles of the control group was significantly lower than in the other groups (p<0.05). These results indicate that chronic ingestion of vitamin E and sesamin attenuated each of elevation in blood pressure, oxidative stress and thrombotic tendency, suggesting that these treatments might be beneficial in the prevention of hypertension and stroke.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Blood Pressure; Blood Vessels; Body Weight; Cerebrovascular Circulation; Cerebrovascular Disorders; Deoxyguanosine; Dioxoles; Disease Susceptibility; Drug Combinations; Genetic Predisposition to Disease; Hypertension; Lignans; Male; Microcirculation; Rats; Rats, Inbred SHR; Stroke; Thrombosis; Vasomotor System; Vitamin E

The effect of sesamin, a lignan from sesame oil, on altered vasodilator and vasoconstrictor responses in aortic rings from deoxycorticosterone acetate (DOCA)-salt-induced hypertensive rats, were examined. The systolic blood pressure after 5-weeks DOCA-salt treatment was 195.0+/-2.8 mmHg, which was much higher than that of sham-operated control animals (131.2+/-2.4 mmHg). Sesamin feeding significantly suppressed the development of this hypertension (167.1+/-8.6 mmHg). Acetylcholine (ACh)-induced endothelium-dependent relaxation of aortic rings was markedly decreased in the DOCA-salt hypertensive animals, compared with cases of the control (pD2, 7.0+/-0.1; maximal response, 64.8+/-3.4% versus pD2, 7.7+/-0.2; maximal response, 93.3+/-2.7%). These changes were partially but significantly improved by the sesamin feeding. This improvement seems to be related to a nitric oxide (NO)-dependent component of ACh-induced action, because sesamin feeding did not affect the responses to ACh in the presence of NO synthase inhibitor. A spontaneous NO releaser (+/-)-(E)-4-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexenamide (NOR 3) which exerts endothelium-independent vasodilatation, produced the same patterns of responses as those observed with ACh in cases of DOCA-salt treatment and sesamin feeding. Phenylephrine-induced vasoconstriction was enhanced by the DOCA-salt treatment, both in preparations with and without endothelium, but these enhancements were almost completely normalized by sesamin feeding. Thus, dietary sesamin could efficiently improve the abnormal vasodilator and vasoconstrictor responses in DOCA-salt hypertensive animals. These effects may contribute to the antihypertensive activity of sesamin.

Topics: Animals; Antihypertensive Agents; Aorta; Body Weight; Desoxycorticosterone; Diet; Dioxoles; Hypertension; In Vitro Techniques; Lignans; Male; Nitric Oxide; Rats; Rats, Sprague-Dawley; Sodium Chloride; Vasoconstriction

The antihypertensive effect of sesamin, a lignan from sesame oil, was examined using salt-loaded and unloaded stroke-prone spontaneously hypertensive rats (SHRSP). The animals at 6 weeks of age were separated into a salt-loaded group and an unloaded group. Salt-loaded animals were maintained on 1% NaCl drinking water. Each group was further divided into two groups: normal-diet group and sesamin-diet group. Systolic blood pressure of all animals was monitored once weekly. At the end of the feeding periods, cardiovascular hypertrophy and renal damage were evaluated. In the salt-loaded group, sesamin feeding significantly suppressed the development of hypertension, and efficient suppression was maintained from 9 to 26 weeks (e.g., 215+/-4 vs. 180+/-4 mmHg, at 17 weeks old). The left ventricle plus septum weight-to-body weight ratio was slightly but significantly lowered by sesamin feeding. When the degree of vascular hypertrophy of the aorta and superior mesenteric artery was histochemically evaluated, wall thickness and wall area of these vessels were significantly decreased by the sesamin feeding. Histological renal damage such as thickening of the tunica intima and fibrinoid degeneration of the arterial wall were often observed in the normal-diet group, but this damage was efficiently reduced in the sesamin-fed animals. On the other hand, in the salt-unloaded group, only a slight and nonsignificant suppressive effect of sesamin on the development of hypertension was observed. Although the wall area of the aorta was significantly decreased by the sesamin feeding, other vascular parameters were not ameliorated. The incidence of histological renal damage tended to decrease in sesamin-fed animals, but these alterations were not statistically significant. Thus, sesamin feeding was much more effective as an antihypertensive regimen in salt-loaded SHRSP than in unloaded SHRSP, thereby suggesting that sesamin is more useful as a prophylactic treatment in the malignant status of hypertension and/or hypertension followed by water and salt retention.

Topics: Animals; Antihypertensive Agents; Blood Pressure; Body Weight; Cardiomegaly; Cerebrovascular Disorders; Diet; Dioxoles; Heart Rate; Hypertension; Kidney; Kidney Diseases; Lignans; Male; Myocardium; Rats; Rats, Inbred SHR

We investigated the antihypertensive effect of sesamin, a lignan from sesame oil, using deoxycorticosterone acetate (DOCA)-salt hypertensive rats. The animals were unilaterally nephrectomized, and then separated into a sham-operated group (sham group) and a DOCA-salt-treated group. The latter was further separated into a normal diet group (control group) and a sesamin-containing diet group (sesamin group). The systolic blood pressure of control group progressively increased in comparison with that of sham group. This DOCA-salt-induced hypertension was markedly suppressed by feeding a sesamin-containing diet. Systolic blood pressure after 5 weeks was 130.6 +/- 1.9 mmHg in the sham group, 198.1 +/- 7.3 mmHg in the control group and 152.5 +/- 8.4 mmHg in the sesamin group, respectively. The treatment with DOCA and salt for 5 weeks significantly increased the weight of the left ventricle plus the septum. However, this increase was significantly suppressed in the sesamin group. When the degree of vascular hypertrophy of the aorta and superior mesenteric artery was histochemically evaluated, there were significant increases in wall thickness, wall area and the wall-to-lumen ratio in the control group, compared with the sham. Sesamin feeding ameliorated the development of DOCA-salt-induced vascular hypertrophy in both the aorta and mesenteric artery. These findings strongly suggest that sesamin is useful as a prophylactic treatment in the development of hypertension and cardiovascular hypertrophy.

Topics: Animals; Antihypertensive Agents; Aorta, Thoracic; Blood Pressure; Cardiomegaly; Desoxycorticosterone; Diet; Dioxoles; Hypertension; Hypertrophy; Lignans; Male; Nephrectomy; Rats; Rats, Sprague-Dawley