In Vivo Evaluation of Dendropanax morbifera Leaf Extract for Anti-Obesity and Cholesterol-Lowering Activity in Mice.

Metabolic syndrome is a worldwide health problem, and obesity is closely related to type 2 diabetes, cardiovascular disease, hypertension, and cancer. According to WHO in 2018, the prevalence of obesity in 2016 tripled compared to 1975. D. morbifera reduces bad cholesterol and triglycerides levels in the blood and provides various antioxidant nutrients and germicidal sub-stances, as well as selenium, which helps to remove active oxygen. Moreover, D. morbifera is useful for treating cardiovascular diseases, hypertension, hyperlipidemia, and diabetes. Therefore, we study in vivo efficacy of D. morbifera to investigate the prevention effect of obesity and cholesterol. The weight and body fat were effectively reduced by D. morbifera water (DLW) extract administration to high-fat diet-fed C57BL/6 mice compared to those of control mice. The group treated with DLW 500 mg∙kg-1∙d-1 had significantly lower body weights compared to the control group. In addition, High-density lipoprotein (HDL) cholesterol increased in the group treated with DLW 500 mg∙kg-1∙d-1. The effect of DLW on the serum lipid profile could be helpful to prevent obesity. DLW suppresses lipid formation in adipocytes and decreases body fat. In conclusion, DLW can be applied to develop anti-obesity functional foods and other products to reduce body fat.

Attenuation of diabetic nephropathy by dietary fenugreek (Trigonella foenum-graecum) seeds and onion (Allium cepa) via suppression of glucose transporters and renin-angiotensin system.

OBJECTIVES: The aim of this study was to determine the effects of dietary fenugreek (Trigonella foenum-graecum) seeds and onion on the hyperglycemia-stimulated glucose transporters and activation of renin-angiotensin system-mediated cascade of events leading to renal lesions in diabetic animals. METHODS: The mechanistic aspects of nephroprotective influence of dietary fenugreek seeds (10%) and onion (3%) on diabetic renal lesions was investigated in streptozotocin diabetic rats. Renal damage was assessed by measuring proteinuria, enzymuria, expression of glucose transporters, renin-angiotensin system, and activities of polyol pathway enzymes. RESULTS: Diabetes resulted in an upregulation of glucose transporters in kidney tissue, which was countered by these dietary interventions. The upregulation of renal angiotensin-converting enzyme and its receptor was also countered by these dietary interventions. Dietary fenugreek and onion significantly reduced metabolites of polyol pathway, nitric oxide, and N-acetyl-ß-d-glucosaminidase activity. Markers of podocyte damage in kidney (nephrin, podocin, and podocalyxin) and their urinary excretion were normalized along with downregulation of the expression of kidney injury molecule-1 by these dietary interventions. Dietary fenugreek and onion effectively countered the diabetes-induced structural abnormalities of renal tissue. CONCLUSION: Feeding fiber-rich fenugreek seeds and sulfur compounds-rich onion produced a blockade in glucose translocation and renin-angiotensin system in the early stage of diabetic nephropathy. This involved a downregulation of the expression of polyol pathway enzymes, partial restoration of the podocyte damage, revival of renal architecture and functional abnormality. The present study also suggested that these two dietary interventions offer a higher renoprotective influence when consumed together.

Exogenous kallikrein protects against diabetic nephropathy.

The kallikrein-kinin system has been shown to be involved in the development of diabetic nephropathy, but specific mechanisms are not fully understood. Here, we determined the renal-protective role of exogenous pancreatic kallikrein in diabetic mice and studied potential mechanisms in db/db type 2 diabetic and streptozotocin-induced type 1 diabetic mice. After the onset of diabetes, mice were treated with either pancreatic kallikrein (db/db+kallikrein, streptozotocin+kallikrein) or saline (db/db+saline, streptozotocin+saline) for 16 weeks, while another group of streptozotocin-induced diabetic mice received the same treatment after onset of albuminuria (streptozotocin'+kallikrein, streptozotocin'+saline). Db/m littermates or wild type mice were used as non-diabetic controls. Pancreatic kallikrein had no effects on body weight, blood glucose and blood pressure, but significantly reduced albuminuria among all three groups. Pathological analysis showed that exogenous kallikrein decreased the thickness of the glomerular basement membrane, protected against the effacement of foot process, the loss of endothelial fenestrae, and prevented the loss of podocytes in diabetic mice. Renal fibrosis, inflammation and oxidative stress were reduced in kallikrein-treated mice compared to diabetic controls. The expression of kininogen1, tissue kallikrein, kinin B1 and B2 receptors were all increased in the kallikrein-treated compared to saline-treated mice. Thus, exogenous pancreatic kallikrein both prevented and ameliorated diabetic nephropathy, which may be mediated by activating the kallikrein-kinin system.

Effects of chronic oral L-arginine administration on the L-arginine/NO pathway in patients with peripheral arterial occlusive disease or coronary artery disease: L-Arginine prevents renal loss of nitrite, the major NO reservoir.

Despite saturation of nitric oxide (NO) synthase (NOS) by its substrate L-arginine (Arg), oral and intravenous supplementation of Arg may enhance NO synthesis, a phenomenon known as "The L-arginine paradox". Yet, Arg is not only a source of NO, but is also a source for guanidine-methylated (N (G)) arginine derivatives which are all inhibitors of NOS activity. Therefore, Arg supplementation may not always result in enhanced NO synthesis. Concomitant synthesis of N (G)-monomethyl arginine (MMA), N (G),N (G)-dimethylarginine (asymmetric dimethylarginine, ADMA) and N (G),N (G´)-dimethylarginine (symmetric dimethylarginine, SDMA) from supplemented Arg may outweigh and even outbalance the positive effects of Arg on NO. Another possible, yet little investigated effect of Arg supplementation may be alteration of renal function, notably the influence on the excretion of nitrite in the urine. Nitrite is the autoxidation product of NO and the major reservoir of NO in the circulation. Nitrite and Arg are reabsorbed in the proximal tubule of the nephron and this reabsorption is coupled, at least in part, to the renal carbonic anhydrase (CA) activity. In the present placebo-controlled studies, we investigated the effect of chronic oral Arg supplementation of 10 g/day for 3 or 6 months in patients suffering from peripheral arterial occlusive disease (PAOD) or coronary artery disease (CAD) on the urinary excretion of nitrite relative to nitrate. We determined the urinary nitrate-to-nitrite molar ratio (UNOxR), which is a measure of nitrite-dependent renal CA activity before and after oral intake of Arg or placebo by the patients. The UNOxR was also determined in 6 children who underwent the Arg test, i.e., intravenous infusion of Arg (0.5 g Arg/kg bodyweight) for 30 min. Arg was well tolerated by the patients of the three studies. Oral Arg supplementation increased Arg (plasma and urine) and ADMA (urine) concentrations. No appreciable changes were seen in NO (in PAOD and CAD) and prostacyclin and thromboxane synthesis (in PAOD). In the PAOD study, UNOxR did not change in the Arginine group (480 ± 51 vs 486 ± 50), but fell in the Placebo group (422 ± 67 vs 332 ± 42, P = 0.025). In the CAD study, UNOxR did not change significantly in the Arginine group (518 ± 77 at start vs 422 ± 40 after 3 months vs 399 ± 66 after 6 months), but fell in the Placebo group (524 ± 69 vs 302 ± 36 vs 285 ± 31; P = 0.025 for 0 vs 3 months). Infusion of Arg tended to decrease the UNOxR in the children (317 ± 41 vs 208 ± 16, P = 0.06). We propose that oral long-term Arg supplementation prevents loss of NO bioactivity by saving nitrite. The optimum Arg dose needs to be elaborated and is likely to be less than 10 g per day in adults. Orally and intravenously administered arginine was well tolerated by the elderly patients and young children, respectively.

The L-arginine/NO pathway and homoarginine are altered in Duchenne muscular dystrophy and improved by glucocorticoids.

The L-arginine/nitric oxide (L-Arg/NO) pathway regulates endothelial function and may play an important role in the pathogenesis of Duchenne muscular dystrophy (DMD). Yet, this pathway is poorly investigated in children suffering from DMD. Endothelial dysfunction can affect the perfusion of contracting muscles, thus leading to ischemia and hypoxia. In the present study, we tested the hypothesis that reduced NO production due to elevated synthesis of N (G),N (G)-dimethyl-L-arginine (asymmetric dimethylarginine, ADMA), an endogenous inhibitor of NO synthesis, is a possible pathophysiological mechanism for progressive intramuscular muscle ischemia and disturbed endothelial function in children with DMD. Given the possible antagonistic action of homoarginine (hArg) on ADMA, we also analyzed this amino acid. We investigated 55 male patients with DMD and 54 healthy male controls (HC; aged 11.9 ± 4.8 vs. 11.1 ± 4.9 years, mean ± SD). Urinary creatinine and metabolites of the L-Arg/NO pathway were measured in plasma and urine by GC-MS or GC-MS/MS. Urine levels of ADMA and its major urinary metabolite dimethylamine (DMA), nitrite and nitrate (P < 0.001 for all) and hArg (P = 0.002) were significantly higher in DMD patients compared to HC, while the urinary DMA/ADMA molar ratio was lower (P = 0.002). In plasma, nitrate (P < 0.001), hArg (P = 0.002) and the hArg/ADMA ratio (P < 0.001) were lower in DMD than in HC. In plasma, ADMA (631 ± 119 vs. 595 ± 129 nM, P = 0.149), arginine and nitrite did not differ between DMD and HC. In DMD, positive correlations between ADMA, DMA or nitrate excretion and the stage of disease (according to Vignos and Thompson) were found. In DMD patients on steroid medication, lower concentrations of ADMA in plasma, and of DMA, ADMA, nitrate and hArg in urine were observed compared to non-treated patients. The L-Arg/NO pathway is impaired in DMD patients, with the disease progression being clinically negatively correlated with the extent of impairment. One of the underlying mechanisms in DMD may involve insufficient antagonism of ADMA by hArg. Steroids, but not creatine supplementation, seems to improve the L-Arg/NO pathway in DMD.

Bioavailability of epicatechin and effects on nitric oxide metabolites of an apple flavanol-rich extract supplemented beverage compared to a whole apple puree: a randomized, placebo-controlled, crossover trial.

SCOPE: Flavanol-rich foods are known to exert beneficial effects on cardiovascular health. The biological effects depend on bioavailability of flavanols which may be influenced by food matrix and dose ingested. We compared the bioavailability and dose-response of epicatechin from whole apple and an epicatechin-rich extract, and the effects on plasma and urinary nitric oxide (NO) metabolites. METHODS AND RESULTS: In a randomized, placebo-controlled, crossover trial, subjects consumed drinks containing 70 and 140 mg epicatechin from an apple extract and an apple puree containing 70 mg epicatechin. Blood and urine samples were collected for 24 h post ingestion. Maximum plasma concentration, AUC(0-24 h) , absorption and urinary excretion were all significantly higher after ingestion of both epicatechin drinks compared with apple puree (p < 0.05). Time to maximum plasma concentration was significantly later for the puree compared with the drinks (p < 0.01). Epicatechin bioavailability was >2-fold higher after ingestion of the 140 mg epicatechin drink compared to the 70 mg epicatechin drink (p < 0.05). Excretion of NO metabolites was higher for all test products compared with placebo, which was significant for the high dose drink (p = 0.016). CONCLUSIONS: Oral bioavailability of apple epicatechin increases at higher doses, is reduced by whole apple matrix and has the potential to increase NO bioavailability.

Preventive effects of hesperidin, glucosyl hesperidin and naringin on hypertension and cerebral thrombosis in stroke-prone spontaneously hypertensive rats.

The effects of hesperidin, glucosyl hesperidin (G-hesperidin), a water-soluble derivative of hesperidin, and naringin on blood pressure and cerebral thrombosis were investigated using stroke-prone spontaneously hypertensive rats (SHRSP). Hesperidin, G-hesperidin and naringin were mixed with diet and fed to the animals for 4 weeks. No effect was evident on body weight, but the supplements significantly suppressed the age related increase in blood pressure. Thrombotic tendency, as assessed using a He-Ne laser technique in the cerebral blood vessels, was significantly decreased in the treated animals compared with the control animals. Measurements of 8-hydroxy-2'-deoxyguanosine (8-OHdG) demonstrated that the supplements had strong antioxidant activity. Furthermore, these supplements significantly increased the production of nitric oxide (NO) metabolites in urine measured with Griess reagent. Vasodilation induced by acetylcholine-mediated NO production in the endothelium was assessed using thoracic aortic ring preparations and indicated that endothelial function was significantly improved by the administration of these supplements. These findings suggest that the strong antioxidant properties of hesperidin, G-hesperidin and naringin could modulate the inactivation of NO and protect endothelial function from reactive oxygen species (ROS). In this manner, the flavonoids could contribute beneficial effects on the mechanisms of hypertension and thrombosis by increasing the bioavailability of NO.

Uroprotective effects of curcumin in cyclophosphamide-induced haemorrhagic cystitis paradigm.

The possible uroprotective effects of curcumin have been addressed in the current study. Haemorrhagic cystitis was induced by challenging male Swiss albino rats with a single dose of cyclophosphamide (150 mg/kg, i.p.). Curcumin (200 mg/kg, i.p.) was administered for 10 consecutive days followed by a single dose of cyclophosphamide. Haemorrhagic cystitis was well characterized morphologically and biochemically. The hallmark of this toxicity was marked congestion, oedema and extravasation in rat urinary bladder, as well as a marked desquamative damage to the urothelium and severe inflammation in the lamina propria. Leucocytic infiltration was also observed and determined by histopathological examination. Serum level of tumour necrosis factor-alpha was notably elevated associated with apparent hypokalaemia and hyponatraemia. Bladder contents of adenosine triphosphate, reduced glutathione and glutathione-S-transferase activity were markedly reduced. Malondialdehyde level, myeloperoxidase activity and urinary nitrite-nitrate levels, expressed as nitric oxide, were dramatically increased. Prior administration of curcumin ahead of cyclophosphamide challenge improved all the biochemical and histologic alterations induced by the cytotoxic drug. Based on these broad findings, it could be concluded that curcumin has proven uroprotective efficacy in this cyclophosphamide haemorrhagic cystitis model, possibly through modulating the release of inflammatory endocoids, namely tumour necrosis factor-alpha and nitric oxide, improving the energy status and restoring the oxidant/antioxidant balance.

Inhibition of natriuretic factors increases blood pressure in rats.

Renal dopamine and nitric oxide contribute to natriuresis during high-salt intake which maintains sodium and blood pressure homeostasis. We wanted to determine whether concurrent inhibition of these natriuretic factors increases blood pressure during high-sodium intake. Male Sprague-Dawley rats were divided into the following groups: 1) vehicle (V)-tap water, 2) NaCl-1% NaCl drinking water, 3) 30 mM l-buthionine sulfoximine (BSO), an oxidant, 4) BSO plus NaCl, and 5) BSO plus NaCl with 1 mM tempol (antioxidant). Compared with V, NaCl intake for 10 days doubled sodium intake and increased urinary dopamine level but reduced urinary nitric oxide content. NaCl intake also reduced basal renal proximal tubular Na-K-ATPase activity with no effect on blood pressure. However, NaCl intake in BSO-treated rats failed to reduce basal Na-K-ATPase activity despite higher urinary dopamine levels. Also, dopamine failed to inhibit proximal tubular Na-K-ATPase activity and these rats exhibited reduced urinary nitric oxide levels and high blood pressure. Tempol supplementation in NaCl plus BSO-treated rats reduced blood pressure. BSO treatment alone did not affect the urinary nitric oxide and dopamine levels or blood pressure. However, dopamine failed to inhibit proximal tubular Na-K-ATPase activity in BSO-treated rats. BSO treatment also increased basal protein kinase C activity, D1 receptor serine phosphorylation, and oxidative markers like malondialdehyde and 8-isoprostane. We suggest that NaCl-mediated reduction in nitric oxide does not increase blood pressure due to activation of D1 receptor signaling. Conversely, oxidative stress-provoked inhibition of D1 receptor signaling fails to elevate blood pressure due to presence of normal nitric oxide. However, simultaneously decreasing nitric oxide levels with NaCl and inhibiting D1 receptor signaling with BSO elevated blood pressure.

Polyphenol-containing azuki bean (Vigna angularis) extract attenuates blood pressure elevation and modulates nitric oxide synthase and caveolin-1 expressions in rats with hypertension.

BACKGROUND AND AIMS: Azuki beans (Vigna angularis) contain polyphenols such as proanthocyanidins that exhibit potential radical scavenging activities. We herein investigated the effects of polyphenol-containing azuki bean extract (ABE) on elevated blood pressure, nitric oxide (NO) production, and expressions of endothelial NO synthase (eNOS), inducible NOS (iNOS), and caveolin-1 proteins in the aorta and kidney of chronically hypertensive rats. METHODS AND RESULTS: Spontaneously hypertensive rats (SHRs/Izm) with approximately 200 mm Hg systolic blood pressure (SBP) were randomly divided into 2 groups fed either 0% or 0.9% ABE-containing diet. Age-matched normotensive Wistar-Kyoto rats were used as the control. The content of 24-h urinary nitrate/nitrite (NOx) excretion was measured to evaluate NO production. After 8 weeks of treatment, the eNOS, iNOS, and caveolin-1 protein expressions in the aorta and kidney were analyzed by western blotting. The SBP of the ABE-treated SHR was significantly lower than that of the untreated SHR. The level of 24-h urinary NOx excretion was significantly higher in the ABE-treated SHR than in the untreated SHR. The eNOS and iNOS expressions in the aorta and kidney were remarkably upregulated in the untreated SHR but suppressed in the ABE-treated SHR. The vascular and renal caveolin-1 expressions were upregulated in the ABE-treated SHR. CONCLUSIONS: ABE reduced the elevated blood pressure and increased NO production in long-term treatment. It may be associated with the modulation of eNOS and iNOS protein expressions in the aorta and kidney during the development of hypertension.

Nitric oxide production in the exhaled air of patients with pulmonary tuberculosis in relation to HIV co-infection.

BACKGROUND: Nitric oxide (NO) is essential for host defense in rodents, but the role of NO during tuberculosis (TB) in man remains controversial. However, earlier observations that arginine supplementation facilitates anti-TB treatment, supports the hypothesis that NO is important in the host defense against TB. Local production of NO measured in fractional exhaled air (FeNO) in TB patients with and without HIV co-infection has not been reported previously. Thus, our aim was to investigate levels of FeNO in relation to clinical symptoms and urinary NO metabolites (uNO). METHODS: In a cross sectional study, FeNO and uNO were measured and clinical symptoms, chest x-ray, together with serum levels of arginine, tumor necrosis factor alpha (TNF-alpha) and interleukin 12 (IL-12) were evaluated in sputum smear positive TB patients (HIV+/TB, n = 36, HIV-/TB, n = 59), their household contacts (n = 17) and blood donors (n = 46) from Gondar University Hospital, Ethiopia. RESULTS: The proportion of HIV-/TB patients with an increased FeNO level (> 25 ppb) was significantly higher as compared to HIV+/TB patients, but HIV+/TB patients had significantly higher uNO than HIV-/TB patients. HIV+ and HIV-/TB patients both had lower levels of FeNO compared to blood donors and household contacts. The highest levels of both uNO and FeNO were found in household contacts. Less advanced findings on chest x-ray, as well as higher sedimentation rate were observed in HIV+/TB patients as compared to HIV-/TB patients. However, no significant correlation was found between FeNO and uNO, chest x-ray grading, clinical symptoms, TNF-alpha, IL-12, arginine levels or sedimentation rate. CONCLUSION: In both HIV negative and HIV co infected TB patients, low levels of exhaled NO compared to blood donors and household were observed. Future studies are needed to confirm whether low levels of exhaled NO could be a risk factor in acquiring TB and the relative importance of NO in human TB.

Thiazide diuretics exacerbate fructose-induced metabolic syndrome.

Fructose is a commonly used sweetener associated with diets that increase the prevalence of metabolic syndrome. Thiazide diuretics are frequently used in these patients for treatment of hypertension, but they also exacerbate metabolic syndrome. Rats on high-fructose diets that are given thiazides exhibit potassium depletion and hyperuricemia. Potassium supplementation improves their insulin resistance and hypertension, whereas allopurinol reduces serum levels of uric acid and ameliorates hypertension, hypertriglyceridemia, hyperglycemia, and insulin resistance. Both potassium supplementation and treatment with allopurinol also increase urinary nitric oxide excretion. We suggest that potassium depletion and hyperuricemia in rats exacerbates endothelial dysfunction and lowers the bioavailability of nitric oxide, which blocks insulin activity and causes insulin resistance during thiazide usage. Addition of potassium supplements and allopurinol with thiazides might be helpful in the management of metabolic syndrome.

[Endothelial function evaluation in salt-sensitive normotensive and mild hypertensive subjects and effects of potassium supplement].

OBJECTIVE: Salt-sensitivity plays an important role in essential hypertension and is associated with more severe target organ injury and higher mortality in patients with essential hypertension. However, the pathologic mechanism of salt-sensitivity is poorly understood and endothelial dysfunction might be involved in salt-sensitive hypertension. We, therefore, observed the endothelial function changes by measuring plasma and urine nitric oxide (NO) concentrations in salt-sensitive (SS) normotensive and mild hypertensive subjects underwent various salt loading protocols and the effects of potassium supplement. METHODS: Thirty-nine normotensive and mild hypertensive subjects (< 160/100 mm Hg), aged 16-60, were enrolled and the study protocol is as follows: 3 days baseline investigation, 1 week low-salt loading (3 g/day), 1 week. high-salt loading (18 g/day) and 1 week high-salt loading plus potassium chloride (4.5 g/day). RESULTS: Plasma and urine NO levels were significantly lower in SS (n = 8) subjects at baseline, low-salt and high-salt loading phases compared with salt-resistant subjects (SR, n = 31) and oral potassium supplement to SS subjects with high salt loading significantly increased plasma and urine NO levels. CONCLUSION: Endothelial function is impaired in normotensive and mild hypertensive SS subjects. Oral potassium supplement could improve endothelial function in normotensive and mild hypertensive SS subjects.

Vitamin E deficiency accelerates nitrate tolerance via a decrease in cardiac P450 expression and increased oxidative stress.

Organic nitrates, such as nitroglycerin (NTG), have been used to relieve the symptoms of angina pectoris. However, their biochemical mechanisms of action, particularly in relation to the development of tolerance, are incompletely defined. It has been reported that supplemental antioxidants such as vitamin E attenuate the development of nitrate tolerance. Therefore, we examined the role of vitamin E in the regulation of nitrate tolerance. Continuous NTG infusion induced nitrate tolerance in rats after 48 h, and vitamin E concentrations decreased in a time-dependent manner in tissues and plasma. Vitamin E supplementation (0.5 g/kg diet) maintained higher concentrations of vitamin E during NTG infusion. The onset and extent of the tolerance, estimated by the decrease in blood pressure following NTG bolus injection during the infusion of NTG, were accentuated in the vitamin E-deficient group. Vitamin E supplementation inhibited nitrate tolerance 48 h after NTG infusion. Cardiac P450 expression (CYP1A2) assessed by immunoblotting, markedly decreased 48 h after NTG administration in control rats. The supplementation of vitamin E significantly attenuated the decrease in P450. Treatment of NTG enhanced vascular superoxide production (L-012 chemiluminescence, DHE fluorescence). The peak of lipid peroxidation and free radical generation in the heart was reached before tolerance developed. In contrast, vitamin E-deficient hearts had lower P450 expression and higher free radical generation than control hearts. To evaluate other vitamin E-inhibitable mechanisms of nitrate tolerance, we studied the NO-cGMP pathway. NTG markedly reduced the vasodilator-stimulated phosphoprotein (VASP) serine 239 phosphorylation (specific substrate of cGMP-activated protein kinase I; cGK-I) in tolerant hearts. Vitamin E inhibited the depletion of pVASP. In conclusion, because continuous NTG infusion causes vitamin E depletion as well as nitrate tolerance, vitamin E deficiency may further accelerate nitrate tolerance via an increase in oxidative stress, the reduced bioconversion because of decreased P450 expression, and impairment of the NO/cGMP pathway in tolerant heart tissues.

Antioxidative and antihypertensive effects of Welsh onion on rats fed with a high-fat high-sucrose diet.

The effects of Welsh onion on the development of hypertension and autoxidation were studied in 6-week-old male Sprague-Dawley rats. The rats were fed with a control diet or a high-fat high-sucrose (HFS) diet with or without 5% Welsh onion (green-leafy type or white-sheath type) for 4 weeks. The systolic blood pressure was elevated and the thiobarbituric acid reactive substances (TBARS) in plasma were increased in the rats fed with the HFS diet without Welsh onion. The rats fed with the HFS diet containing Welsh onion, especially the green-leafy type, had lower blood pressure. They also had a higher level of nitric oxide (NO) metabolites in both the urine and plasma, lower activity of NADH/NADPH oxidase in the aorta, and suppressed angiotensin II production. The effect of white Welsh onion on decreasing the blood pressure was not significant, although the effects on increasing NO metabolites in the urine and decreasing NADH oxidase activity in the aorta were significant. The TBARS value in the plasma was lowered in the rats fed with either green or white Welsh onion, but the in vitro radical scavenging and ferric reducing antioxidative activities were much higher with green Welsh onion than with the white type. These results suggest that the green-leafy Welsh onion, but not the white type, reduced superoxide generation by suppressing the angiotensine II production and then the NADH/NADPH oxidase activity, increasing the NO availability in the aorta, and consequently lowering the blood pressure in the rats fed with the HFS diet. The radical scavenging and reducing antioxidative activities of green Welsh onion may also be effective in decreasing superoxide.

Effects of prolonged oral supplementation with l-arginine on blood pressure and nitric oxide synthesis in preeclampsia.

BACKGROUND: Several lines of evidence point to the dysfunction of the endothelial l-arginine-NO system in preeclampsia. We investigated the influence of dietary supplementation with l-arginine on blood pressure and biochemical measures of NO production in women with preeclampsia in prospective, randomized, placebo-controlled study. DESIGN: The 61 preeclamptic women on a standardized low nitrate diet received orally 3 g of l-arginine (n = 30) or placebo (n = 31) daily for 3 weeks as a supplement to standard therapy. The differences between the two groups in systolic (SBP), diastolic (DBP) and mean arterial blood pressures (MAP) as well as in plasma levels of selected aminoacids, plasma concentrations of nitrates/nitrites (NOx) and in 24-h urine NOx excretion were determined. RESULTS: After 3 weeks of treatment, values of SBP, DPB and MAP were significantly lower in the group taking l-arginine as compared with the placebo group (SBP: 134.2 +/- 2.9 vs. 143.1 +/- 2.8; DBP: 81.6 +/- 1.7 vs. 86.5 +/- 0.9; MAP: 101.8 +/- 1.5 vs. 108.0 +/- 1.2 mmHg, P < 0.01). Importantly, treatment with exogenous l-arginine significantly elevated 24-h urinary excretion of NOx and mean plasma levels of l-citrulline. Exogenous l-arginine did not influence plasma concentrations of l-arginine, l-ornithine and methylated arginines (ADMA, SDMA, L-NMMA). CONCLUSIONS: We conclude that in women with preeclampsia, prolonged dietary supplementation with l-arginine significantly decreased blood pressure through increased endothelial synthesis and/or bioavailability of NO. It is tempting to speculate that the supplementary treatment with l-arginine may represent a new, safe and efficient strategy to improve the function of the endothelium in preeclampsia.

Effects of boiling on the antihypertensive and antioxidant activities of onion.

This study was designed to show the effect of boiling on the antihypertensive and antioxidant activities of onion in N(G)-nitro-L-arginine methyl ester (L-NAME) induced-hypertensive rats and spontaneously hypertensive rats (SHR). Male 6-wk-old Sprague-Dawley rats were made hypertensive by being given distilled water containing L-NAME at a dose of 50 mg/kg BW/d. These rats were fed diets containing raw or boiled onion at a concentration of 5%. Raw onion significantly reduced the increase in systolic blood pressure in both L-NAME induced-hypertensive rats and SHR, and inhibited the increase in thiobarbituric acid-reactive substances (TBARS) and conjugated dienes in the plasma and tissues of SHR. The antihypertensive effect of boiled onion was not found, and the antioxidant activity of it was much weaker than that of raw onion. The excretion of nitric oxide metabolites (NOx) in urine was enhanced by raw onion in both L-NAME induced-hypertensive rats and SHR, and was enhanced by boiled onion only in SHR. In conclusion, our results suggested that the anti-hypertensive activity of onion disappeared during boiling, and the disappear of the antihy-pertensive activity of raw onion after boiling might come, in part, from a decrease of the antioxidative activity of onion, with a consequent reduction in the saving of nitric oxide (NO).

Black and green tea polyphenols attenuate blood pressure increases in stroke-prone spontaneously hypertensive rats.

Oxidative stress was reported to be involved not only in cardiovascular diseases, but also in hypertension. Epidemiologic studies indicated that tea consumption slightly reduces blood pressure. We conducted two studies to determine whether black and green tea can lower blood pressure (BP) in stroke-prone spontaneously hypertensive rats (SHRSP). Male SHRSP (n=15) were allowed to recover for 2 wk after a transmitter for measuring BP was implanted in the peritoneal cavity. The rats were divided into three groups: the control group consumed tap water (30 mL/d); the black tea polyphenol group (BTP) consumed water containing 3.5 g/L thearubigins, 0.6 g/L theaflavins, 0.5 g/L flavonols and 0.4 g/L catechins; and the green tea polyphenol group (GTP) consumed water containing 3.5 g/L catechins, 0.5 g/L flavonols and 1 g/L polymetric flavonoids. The telemetry system was used to measure BP, which were recorded continuously every 5 min for 24 h. During the daytime, systolic and diastolic BP were significantly lower in the BTP and GTP groups than in the controls. Protein expressions of catalase and phosphorylated myosin light chain (MLC-p) were measured in the aorta by Western blotting. GTP significantly increased catalase expression, and BTP and GTP significantly decreased MLC-p expression in the aorta. These data demonstrate that both black and green tea polyphenols attenuate blood pressure increases through their antioxidant properties in SHRSP. Furthermore, because the amounts of polyphenols used in this experiment correspond to those in approximately 1 L of tea, the regular consumption of black and green tea may also provide some protection against hypertension in humans.

Supplementation of L-arginine improves hypertension and lipid metabolism but not insulin resistance in diabetic rats.

Nitric oxide (NO) plays an important role in glucose and lipid metabolism. We previously reported that NO synthesis inhibitors, such as NG-nitro-L-arginine methyl ester (L-NAME), deteriorate insulin sensitivity and lipid metabolism, while the addition of L-arginine reverses this deterioration. L-arginine is a precursor of NO, and is used as a supplement in the US. In the present study, we evaluated whether the administration of L-arginine alone improves insulin resistance and serum lipid levels in insulin-resistant and hypertriglycemic rat models. Diabetic rats were divided into 3 groups: the control (Cont) group (standard diet), the L-NAME group (diet containing L-NAME), and the Arg group (diet containing L-arginine). After 4 weeks of breeding, urinary NOx, glucose infusion rate (GIR), glucose and lipid tolerance tests were performed. Urinary NOx levels were significantly lower in the L-NAME group than in the Cont group. The GIR in the L-NAME group was significantly lower than that in the Cont group, suggesting increased insulin resistance. However, the administration of L-arginine did not influence insulin resistance in the Arg group. Oral lipid administration significantly increased plasma triglyceride levels in the L-NAME group and plasma triglyceride levels were significantly lower in the Arg group than in the Cont group. The area under the curve of plasma triglyceride levels after oral lipid administration was larger in the L-NAME group than in the Cont group. The administration of L-NAME increased insulin resistance and decreased lipid metabolism. L-arginine significantly increased urinary NO secretion but did not improve insulin resistance, although it did improve lipid metabolism. These findings suggest that supplementation of L-arginine cannot improve insulin resistance in diabetic rats probably due to increased insulin secretion by L-arginine.

Antihypertensive effects of onion on NO synthase inhibitor-induced hypertensive rats and spontaneously hypertensive rats.

This study was designed to show the effects of onion on blood pressure in N(G)-nitro-L-arginine methyl ester (L-NAME) induced-hypertensive rats and stroke prone spontaneously hypertensive rats (SHRSP) using dried onion at 5% in their diets. For the experiment with L-NAME induced-hypertensive rats, male 6-weeks-old Sprague-Dawley rats were given tap water containing L-NAME to deliver 50 mg/kg BW/day. In this experiment, we found distinct antihypertensive effects of onion on the L-NAME induced-hypertensive rats and the SHRSP. Dietary onion decreased the thiobarbituric acid reactive substances (TBARS) in plasma in these hypertensive rats. Also, onion increased the nitrate/nitrite (products of nitric oxide (NO)) excreted in urine and the NO synthase (NOS) activity in the kidneys in SHRSP. These results suggested that the increased NO caused by the greater NOS activity, and additionally by the increased saving of NO by the antioxidative activity of onion, was one of the cause of the antihypertensive effect of onion in SHRSP. In the L-NAME induced hypertensive rats, onion did not significantly block the inhibition of NOS activity by L-NAME, and decreased nitrate/nitrite excretion in urine was not restored. The mechanism of the antihypertensive effect of onion probably involves increased saving of NO by antioxidative activity of onion in L-NAME induced-hypertensive rats.