L-arginine Group Research Articles

Effects of L-arginine Supplementation and Aerobic Training on Hemodynamic Indices of Obese Men

Background: L-arginine is a precursor to nitric oxide, which can affect some hemodynamic indices. Objectives: The purpose of this study was to investigate the effect of one-month aerobic training with and without supplementation of L-arginine on hemodynamic indices in obese men. Methods: A quasi-experimental double-blind, study was carried out. Subjects (age, 30 - 45 years; BMI, 38 - 40 kg.m-2) were randomly assigned to an exercise and L-arginine supplementation group (n = 10) and placebo group (n = 10). Before and after four weeks of aerobic exercise (three 90 - 120 min sessions per week at 65% - 85% of maximal heart rate), systolic and diastolic blood pressure, and rate pressure product (RPP) were measured at rest. The analysis of variance was used to determine the interaction between the two factors of exercise and supplementation of L-arginine on the dependent variables at P < 0.05. Results: Four weeks of aerobic exercise reduced the RPP in both groups (P ≤ 0.05), while the L-arginine group significantly reduced systolic blood pressure (116.6 ± 3.40), diastolic blood pressure (76 ± 2.29) and RPP (8918.2 ± 722.86). Conclusions: L-arginine supplementation along with four weeks of aerobic exercise can be effective in controlling hypertensive of obese men.

Standard therapy potentiation of patients with Stable Angina FC III with concomitant Hypertension through nitric oxide donator L-arginine administration

The purpose of the study was to improve treatment of patients with Stable Angina functional class III (FC) with concomitant arterial hypertension (AH) through a combination of standard therapy with L-arginine. There were examined63 patients with Stable Angina III FK with AH. All patients in the clinic were analyzedby the test with reactive hyperemia, were measured levels of cardio-ankle vascular index, pulse wave velocity, aortic stiffness index and the thickness of the complex "intima-media". It has been established that in studied patients with L-arginine significantly improves endothelium dependent vasodilatation, presumably due to the supply of substrate for the synthesis of nitric oxide, as well as due to antioxidant properties, which prevents the excessive formation of toxic peroxynitrite in conditions of high oxidation stress. Endothelial-independent vasodilation in the standard therapy group was significantly lowered, while in the L-arginine group, the incidence of changes was unreliable, which may indicate a decrease in sensitivity to nitrates in Group I. Thus, the inclusion to antianginal and antihypertensive therapyof L-arginine is more pronouncedaffects subclinical parameters of arterial rigidity, than in the background of treatment with standard therapy.

Standard therapy potentiation of patients with Stable Angina FC III with concomitant Hypertension through nitric oxide donator L-arginine administration

The purpose of the study was to improve treatment of patients with Stable Angina functional class III (FC) with concomitant arterial hypertension (AH) through a combination of standard therapy with L-arginine. There were examined63 patients with Stable Angina III FK with AH. All patients in the clinic were analyzedby the test with reactive hyperemia, were measured levels of cardio-ankle vascular index, pulse wave velocity, aortic stiffness index and the thickness of the complex "intima-media". It has been established that in studied patients with L-arginine significantly improves endothelium dependent vasodilatation, presumably due to the supply of substrate for the synthesis of nitric oxide, as well as due to antioxidant properties, which prevents the excessive formation of toxic peroxynitrite in conditions of high oxidation stress. Endothelial-independent vasodilation in the standard therapy group was significantly lowered, while in the L-arginine group, the incidence of changes was unreliable, which may indicate a decrease in sensitivity to nitrates in Group I. Thus, the inclusion to antianginal and antihypertensive therapyof L-arginine is more pronouncedaffects subclinical parameters of arterial rigidity, than in the background of treatment with standard therapy.

Pathophysiological changes in experimental polycystic ovary syndrome in female albino rats: Using either hemin or L-arginine.

Polycystic ovary syndrome (PCOS), one of the important endocrine disorders affecting females in the reproductive age, is caused mainly by an abnormal oxidation status that subsequently causes inflammatory conditions. Thus, this study aims to examine the possible individual prophylactic effects of gasotransmitters, hemin, or L-arginine in letrozole-induced PCOS. Fifty adult female albino rats were used and separated into a control group, which received the vehicle; a letrozole-induced PCOS group (L), which received letrozole orally at a dose level of 1 mg/kg for 21 days; a letrozole+hemin (L+H) group, which received letrozole plus hemin at a dose level of 25 mg/kg injected IP twice per week for 21 days; and a letrozole+L-arginine (L+A) group, which received letrozole plus L-arginine at a dose level of 200 mg/kg orally for 21 days. During PCO induction, the body weight and Lee index were measured. Serum glucose, insulin, lipid profile, gonadotrophic hormones, testosterone, estrogen, and tumor necrosis factor alpha were assayed, while ovarian tissues were analyzed to measure the oxidative state and histopathological changes. Our results proved that either hemin or L-arginine administration could improve the oxidative state, the inflammatory reaction, the hormonal imbalance, and the metabolic disturbances in PCO rats, which was confirmed by a histopathological examination of the rats' ovaries. In conclusion, either hemin or L-arginine had protective effects against PCOS with better pathophysiological changes with hemin.

Effects of Watermelon Powder and l-arginine Supplementation on Azoxymethane-Induced Colon Carcinogenesis in Rats

Diets high in fruits and vegetables may help prevent colorectal cancer (CRC). Watermelon consumption may reduce CRC risk due to its concentration of l-citrulline and its role in endothelial nitric oxide (NO) production. Research suggests that increased NO levels have tumoricidal effects. The purpose of this study was to determine the effects of watermelon powder supplementation on aberrant crypt foci (ACF) formation, precancerous lesions, and expression of genes associated with colon carcinogenesis. Thirty-two male Sprague-Dawley rats were assigned into three groups: control, 0.36% l-arginine, or 0.5% watermelon powder and injected with azoxymethane (15 mg/kg body weight). Both l-arginine and watermelon powder groups exhibited lower total numbers of ACF and high multiplicity ACF (P < 0.01). The watermelon powder group exhibited higher NO levels and lower 8-hydroxyguanosine DNA damage (P < 0.05). Watermelon powder and l-arginine downregulated 8-oxoguanine DNA glycosylase gene expression and upregulated O6-methylguanine DNA methyltransferase gene expression (P < 0.05). Cyclooxgenase-2 gene expression was lower for rats fed with watermelon powder (P < 0.05). These results suggest that watermelon powder or l-arginine supplementation may reduce the risk of colon cancer by suppressing ACF formation through lowering oxidative DNA damage and inflammation, modulating DNA repair enzyme expression, and/or enhancing NO production.

Dietary l-arginine Supplementation Alleviates the Intestinal Injury and Modulates the Gut Microbiota in Broiler Chickens Challenged by Clostridium perfringens.

Our previous reports suggested that Dietary l-arginine supplementation attenuated gut injury of broiler chickens infected with Clostridium perfringens by enhancing intestinal immune responses, absorption and barrier function, but its effect on the gut microbiome of broiler chickens remains unclear. This experiment aimed at evaluating the effects of Dietary l-arginine supplementation on the gut bacterial community composition and function of broiler chickens challenged with C. perfringens. In total, 105 1-day-old male Arbor Acres broiler chickens were assigned to three groups: Control (CTL), C. perfringens-challenged (CP), and C. perfringens-challenged and fed diet supplemented with 0.3% l-arginine (ARGCP) groups. The challenge led to macroscopic and histomorphological gut lesions, decreased villus height and increased the number of Observed species, Shannon, Chao1 and ACE indices of ileal microbiota, whereas l-arginine addition reversed these changes. Moreover, the three treatments harbored distinct microbial communities (ANOSIM, P < 0.05). At the genus level, 24 taxa (e.g., Nitrosomonas spp., Coxiella spp., Ruegeria spp., and Thauera spp.) were significantly more abundant in CP group than in CTL group (P < 0.05), whereas the levels of 23 genera of them were significantly decreased by l-arginine supplementation (P < 0.05). The abundances of only 3 genera were different between CTL and ARGCP groups (P < 0.05). At the species level, the challenge promoted the relative abundance of Nitrospira sp. enrichment culture clone M1-9, Bradyrhizobium elkanii, Nitrospira bacterium SG8-3, and Pseudomonas veronii, which was reversed by l-arginine supplementation (P < 0.05). Furthermore, the challenge decreased the levels of Lactobacillus gasseri (P < 0.05). Predictive functional profiling of microbial communities by PICRUSt showed that compared with CP group, ARGCP group had enriched pathways relating to membrane transport, replication and repair, translation and nucleotide metabolism and suppressed functions corresponding to amino acid and lipid metabolisms (P < 0.05). The relative abundances of KEGG pathways in l-arginine-fed broilers were almost equal to those of the controls. In conclusion, l-arginine alleviated the gut injury and normalized the ileal microbiota of C. perfringens-challenged chickens to resemble that of unchallenged controls in terms of microbial composition and functionality.

Thermodynamic and thermal properties of the C60-l-Arg derivative

The paper presents experimental and DFT simulated data on temperature dependence of heat capacity for C60-l-arginine derivative. Smoothed Cp,m∘Tvalues in the temperature range from T → 0 K to 320 K are presented along with the values of standard thermodynamic functions: Sm°, [Hm∘T-Hm∘0] and [Φm∘T-Φm∘0]. In addition, the molar third law entropy and the molar formation entropy of the C60-l-arginine derivative in crystalline state at T = 298.15 K are calculated. The data on complex thermal analysis reveal that the C60-l-arginine derivative is stable up to 340 K. Further increasing of temperature leads to destruction of l-arginine groups and oxidation of fullerene core.

The essential role of hypothalamic paraventricular nucleus nNOS in the modulation of autonomic control in exercised rats

Nitric oxide (NO), an intercellular signaling molecule is relevant for circulatory autonomic control. Brain NO synthase (NOS) and NO levels were downregulated in pathological conditions, but rescued after exercise training. We hypothesized that exercise training was also able to improve NO modulation within the hypothalamic paraventricular nucleus (PVN) of healthy rats. Male Wistar rats were submitted to two 4-weeks protocols: i) swimming training (T) or kept sedentary (S), ii) l-arginine (62,5 mg/mL, 1 mL/day p. o.) or vehicle supplementation. Rats underwent stereotaxic surgery (PVN bilateral guide cannulas) and chronic catheterization of artery/vein. Arterial pressure (AP), heart rate (HR) and baroreflex sensitivity were recorded in conscious rats at rest and following a selective nNOS inhibitor (Nw-Propyl-l-Arginine, 4 nmol/100 nL) within the PVN. Rats were deeply anesthetized for brain perfusion/harvesting after respiratory arrest. In separate groups (T and S, l-arginine and Vehicle supplemented) not submitted to PVN cannulation, fresh and fixed brains were obtained for gene and protein nNOS expression (qPCR and immunohistochemistry) and nitrite levels (Griess reaction). T and l-arginine treatment were accompanied by resting bradycardia, augmented parasympathetic and reduced sympathetic activity to heart and vessels (power spectral analysis) and increased baroreflex sensitivity (†P < 0.05). In contrast, PVN nNOS inhibition blocked/attenuated these effects in addition to significantly increase in resting MAP and HR (with larger effects in T and l-arginine treated rats vs. respective controls, †P < 0.05). T increased nNOS gene and protein expression within the ventromedial and posterior PVN nuclei (†P < 0.05). PVN nitirite levels were also increased in T and l-arginine groups (†P < 0.05). Data strongly suggest that training by increasing NO availability within PVN preautonomic nuclei favors both the slow down of sympathetic and the augmentation of parasympathetic activity and facilitates baroreflex control, therefore improving autonomic regulation of the heart in healthy rats.

Watermelon and l-arginine consumption improve serum lipid profile and reduce inflammation and oxidative stress by altering gene expression in rats fed an atherogenic diet

Watermelon (Citrullus lanatus) is rich in l-citrulline, an l-arginine precursor that may reduce cardiovascular disease risk. The purpose of this study was to compare the effects of watermelon powder and l-arginine on lipid profiles, antioxidant capacity, and inflammation in rats fed an atherogenic diet. We hypothesized that watermelon and l-arginine would increase antioxidant capacity and reduce blood lipids and inflammation by modulating hepatic gene expression. Male Sprague-Dawley rats aged 21 days (N = 32) were assigned to 3 groups and fed diets containing watermelon powder (0.5% wt/wt), l-arginine (0.3% as 0.36% l-arginine HCl wt/wt), or a control diet for 9 weeks. Watermelon and l-arginine supplementation improved lipid profiles by lowering serum concentrations of triglycerides, total cholesterol, and low-density lipoprotein cholesterol (P < .050). Serum concentrations of C-reactive protein were significantly lower (P < .050) in the watermelon and l-arginine groups. Rats in the watermelon and l-arginine groups showed reduced oxidative stress, increased total antioxidant capacity, and higher concentrations of superoxide dismutase and glutathione S-transferase (P < .050). Concentrations of aspartate aminotransferase, alkaline phosphatase, and lactate dehydrogenase were lower (P < .050) in the watermelon and l-arginine groups. Watermelon and l-arginine consumption upregulated hepatic gene expression of endothelial nitric oxide synthase and downregulated expression of fatty acid synthase, 3-hydroxy-3-methylglutaryl-CoA reductase, sterol regulatory element-binding protein 1, sterol regulatory element-binding protein 2, cyclooxygenase-2, and nuclear factor–κB p65 (P < .050). The results support the hypothesis that watermelon and arginine improve cardiovascular disease risk factors including lipid profile, antioxidant capacity, and inflammation by altering relevant gene expression.

Fasudil hydrochloride ameliorates memory deficits in rat model of streptozotocin-induced Alzheimer’s disease: Involvement of PI3-kinase, eNOS and NFκB

Restoration of PI3-kinase signaling portrays therapeutic potential in Alzheimer’s disease (AD). Hyperactive Rho-kinase in AD negatively modulates PI3-kinase pathway, thereby cause cognitive decline. Fasudil is a Rho-kinase inhibitor that has shown therapeutic benefits in brain disorders. The present study is aimed to decipher the role of PI3-kinase pathway in neuroprotective activity of fasudil using STZ-ICV model of AD. MWM and NORT showed that fasudil (300 μg/kg, ICV) averted the STZ-ICV (3 mg/kg) induced memory dysfunctions in rats. Wortmannin (5 μg/rat) or l-NAME (20 mg/kg) attenuated the memory restorative function of fasudil in STZ treated rats. However, l-Arginine (50 mg/kg) group exhibited marked improvement in memory functions. Markers of oxidative stress (TBARS, GSH, SOD, CAT), nitrite, AChE, TNF-α, eNOS and NFκB were measured in whole brain of rats. STZ-ICV group exhibited significant elevation in brain oxidative stress, AChE activity, TNF-α, NFκB expression and decrease in eNOS level. These effects of STZ were effectively ameliorated by administration of fasudil for 21 days. Wortmannin (PI3-kinase inhibitor) or l-NAME (NOS blocker) attenuated the antioxidative, anti-inflammatory and cholinergic activities of fasudil. Although brain nitrite content was decreased by l-NAME and wortmannin, the l-NAME group depicted rise in eNOS content (not activity) and NFκB expression, whereas, decrease in same was observed in wortmannin group. l-Arginine lowered the brain oxidative stress, inflammation, AChE activity, eNOS expression (not activity), NFκB levels and elevated nitrite content. In STZ-ICV rat model of AD, fasudil (Rho-kinase inhibitor) ameliorated the AD symptoms by reinstating PI3-kinase mediated upregulation of eNOS and control over brain NFκB activity.

Effects of Chronic Lithium Chloride and L-Arginine Treatment on Prevention of Streptozotocin Induced Cognitive Deficits by Ellagic Acid

Administration of streptozotocin (STZ) through intracerebroventricular (ICV) route manifests AD symptoms in rats. STZ deregulates the control over GSK-3 and eNOS activities through disruption of phosphoinositides mediated signaling. We attempted to elucidate the functions of GSK-3 and eNOS in memory enhancing activity of ellagic acid (EGA) in STZ (ICV) triggered AD type dementia. A 3 mg/kg dose of STZ was injected gently in lateral cerebral ventricles of rats on day 1 and 3. The rats were given EGA (35 mg/kg b.w.) through oral route for four weeks daily. LiCl (GSK-3 inhibitor) and L-Arginine (NO precursor) were administered for four weeks to explore the modulation of GSK-3 and eNOS respectively by EGA in STZ (ICV) injected rats. MWM and EPM paradigms were utilized for evaluation of memory of rats. The rats were sacrificed on day 28 to determine markers of oxidative stress (TBARS, GSH, SOD, CAT), nitrite, AChE, LDH, TNF-α and eNOS in brain. STZ (ICV) initiated cognitive deficits through enhancement of brain oxidative stress, nitrite, TNF-α, AChE, LDH activity and reduction in eNOS levels. EGA attenuated the rise in oxidative stress, inflammation and LDH activity in STZ (ICV) treated rats. Decrease in nitrite content, AChE activity and resurrection of eNOS activity by EGA averted STZ (ICV) induced memory dysfunction in rats. Chronic inhibition of GSK-3 by LiCl (100 mg/kg, i.p.) enhanced these effects of EGA in STZ (ICV) injected rats which thereby exhibited marked cognitive improvement. L-Arginine group manifested inflation in brain oxidative stress, TNF-α content, AChE and LDH activities. L-Arginine (200 mg/kg, i.p.) surged the nitrite content even though eNOS expression was diminished in brain of EGA and STZ (ICV) administered rats resulting in profound loss of memory. It can be concluded that GSK-3 and eNOS are involved in memory enhancing activity of EGA in STZ (ICV) injected rats.

Caffeic acid phenethyl ester rescued streptozotocin-induced memory loss through PI3-kinase dependent pathway

The present study was undertaken to elucidate the role of PI3-kinase signaling in memory enhancing potential of caffeic acid phenethyl ester (CAPE) against cognitive defects in rats after centrally administered streptozotocin as a model of Alzheimer’s disease. The Morris water maze and elevated plus maze paradigms showed profound loss of memory in adult Wistar rats (180–200 g) injected with streptozotocin (3 mg/kg) bilaterally (STZ-ICV) on day 1 and 3. Intraperitoneal administration of CAPE (6 mg/kg, i.p., 28 days) attenuated STZ-ICV triggered memory loss in rats. Treatment with PI3-kinase inhibitor (wortmannin, 5 μg/rat, ICV) or NOS blocker (L-NAME, 20 mg/kg, i.p., 28 days) interfered with memory restorative function of CAPE in STZ treated rats. In biochemical analysis markers of oxidative stress (TBARS, GSH, SOD, CAT), nitrite, AChE, TNF-α, eNOS and NFκB were measured in brain of rats on day 28. Interestingly, L-Arginine (100 mg/kg, i.p., 28 days) group exhibited moderate (p > 0.05) decline in memory functions. The brain oxidative stress, TNF-α, AChE activity and NFκB levels were elevated, and eNOS level was lowered by STZ-ICV treatment. Administration of CAPE lowered oxidative stress, AChE, nitrite and TNF-α levels in brain of rats. The eNOS level was enhanced and NFκB level was decreased by CAPE in STZ treated rats. Wortmannin injection elevated the brain oxidative stress, AChE activity and TNF-α levels, and decreased the nitrite, eNOS and NFκB level. Rise of brain oxidative stress parameters, AChE activity, TNF-α, eNOS and NFκB levels, and decline in brain nitrite content was observed in L-NAME treated group. L-Arginine administration showed modest effects (p > 0.05) on oxidative stress parameters. Brain nitrite content was enhanced although eNOS, NFκB levels, and AChE activity was decimated by L-Arginine treatment. It can be concluded that PI3-kinase mediated nitric oxide facilitation is an essential feature of CAPE action in STZ-ICV treated rats.

Effects of nutrient restriction and arginine treatment on oxidative stress in the ovarian tissue of ewes during the luteal phase

The aim of this study was to determine whether nutrient restriction and arginine treatment affect energy metabolism changes and oxidative stress through the mitochondrial pathway in the ovarian tissue of ewes during the luteal phase. On days 6–15 of the estrous cycle, 24 multiparous Hu sheep (BW = 43.56 ± 1.53 kg) were randomly assigned to three groups: control group (CG; n = 6), restriction group (RG; n = 9), and l-arginine group (AG; n = 9) administered Arg treatment (or vehicle) three times per day. The ewes were slaughtered at the end of treatment, and blood samples and ovaries were collected for analysis. In this study, the expression levels of antioxidase enzymes (SOD2, CAT and GPX1) and mitochondrial biogenesis-related genes (ESRRA and TFAM), as well as antioxidase activity and mitochondrial function were examined in ovarian tissue. Nutrient restriction resulted in activation of ESRRA and TFAM and an increase in relative mtDNA copy number, whereas arginine treatment led to a pronounced recovery of ovarian tissue. In addition, we observed increased AMPK phosphorylation at Thr172 and SIRT3 levels in nutrient restricted ewes, and these effects decreased with arginine treatment. In conclusion, the present results indicated that short-term nutritional restriction led to changes in energy metabolism and oxidative stress. These changes disrupted the redox balance, thus leading to apoptosis through the mitochondria-dependent apoptosis pathway. Arginine treatment altered gene expression in ovarian tissue and increased the resistance to oxidative stress and the anti-apoptosis capacity. The results presented here suggest a potential method to increase agricultural productivity and economic benefits in the sheep industry by using dietary supplementation with arginine to decrease temporary undernutrition of ewes.

The possible protective effect of L-arginine against 5-fluorouracil-induced nephrotoxicity in male albino rats.

5-fluorouracil (5-FU) is a potent antineoplastic agent used for the treatment of various malignancies. The L-arginine nitric oxide (NO) pathway involved in the pathogenesis of chemotherapy induced kidney damage. This work investigated the beneficial mechanism of L-arginine supplementation in 5-FU induced nephropathy. Eighty male Wistar rats were divided into four equal groups: control group; L-arginine group (378 mg/rat/day for 4 weeks); 5-FU group (189 mg/rat/week for 4 weeks) and L-arginine for 1 week before and 4 weeks concomitant with 5-FU group. At the end of experiment, the kidney functions were assessed and kidneys specimens were processed for paraffin sections and stained with haematoxylin and eosin (H&E), Masson's trichome (MT) and periodic acid-Schiff (PAS) stains. Other sections were processed for immunohistochemical demonstration of caspase-3 and inducible NO synthase (iNOS). Image analyser was used to analyse the results morphometrically and statistically. L-arginine administration to 5-FU treated animals elicited significant reduction in serum urea and creatinine levels, urine volume, urinary protein excretion and kidney/body weight ratio in comparison to fluorouracil treated group. L-arginine improved glomeruloscelerosis, degeneration of convoluted tubules and interstitial fibrosis in 5-FU treated animals. L-arginine attenuated effectively some biochemical and histological changes in 5-FU nephrotoxicity.

Decreased diabetes risk over 9\xa0year after 18-month oral l-arginine treatment in middle-aged subjects with impaired glucose tolerance and metabolic syndrome (extension evaluation of l-arginine study)

PurposeThis study aimed to determine whether l-arginine supplementation lasting for 18 months maintained long-lasting effects on diabetes incidence, insulin secretion and sensitivity, oxidative stress, and endothelial function during 108 months among subjects at high risk of developing type 2 diabetes.MethodsOne hundred and forty-four middle-aged subjects with impaired glucose tolerance and metabolic syndrome were randomized in 2006 to an l-arginine supplementation (6.4 g orally/day) or placebo therapy lasting 18 months. This period was followed by a 90-month follow-up. The primary outcome was a diagnosis of diabetes during the 108 month study period. Secondary outcomes included changes in insulin secretion (proinsulin/c-peptide ratio), insulin sensitivity (IGI/HOMA-IR), oxidative stress (AOPPs), and vascular function. After the 18 month participation, subjects that were still free of diabetes and willing to continue their participation (104 subjects) were further followed until diabetes diagnosis, with a time span of about 9 years from baseline.ResultsAlthough results derived from the 18 month of the intervention study demonstrated no differences in the probability of becoming diabetics, at the end of the study, the cumulative incidence of diabetes was of 40.6% in the l-arginine group and of 57.4% in the placebo group. The adjusted HR for diabetes (l-arginine vs. placebo) was 0.66; 95% CI 0.48, 0.91; p < 0.02). Proinsulin/c-peptide ratio (p < 0.001), IGI/HOMA-IR (p < 0.01), and AOPP (p < 0.05) levels were ameliorated in l-arginine compared to placebo.ConclusionsThese results may suggest that the administration of l-arginine could delay the development of T2DM for a long period. This effect could be mediated, in some extent, by l-arginine-induced reduction in oxidative stress.

Muscle synergies and activation in Nordic walking compared with conventional walking

Nitric oxide (NO), an intercellular signaling molecule is relevant for circulatory autonomic control. Brain NO synthase (NOS) and NO levels were downregulated in pathological conditions, but rescued after exercise training. We hypothesized that exercise training was also able to improve NO modulation within the hypothalamic paraventricular nucleus (PVN) of healthy rats. Male Wistar rats were submitted to two 4-weeks protocols: i) swimming training (T) or kept sedentary (S), ii) l-arginine (62,5 mg/mL, 1 mL/day p. o.) or vehicle supplementation. Rats underwent stereotaxic surgery (PVN bilateral guide cannulas) and chronic catheterization of artery/vein. Arterial pressure (AP), heart rate (HR) and baroreflex sensitivity were recorded in conscious rats at rest and following a selective nNOS inhibitor (Nw-Propyl-l-Arginine, 4 nmol/100 nL) within the PVN. Rats were deeply anesthetized for brain perfusion/harvesting after respiratory arrest. In separate groups (T and S, l-arginine and Vehicle supplemented) not submitted to PVN cannulation, fresh and fixed brains were obtained for gene and protein nNOS expression (qPCR and immunohistochemistry) and nitrite levels (Griess reaction). T and l-arginine treatment were accompanied by resting bradycardia, augmented parasympathetic and reduced sympathetic activity to heart and vessels (power spectral analysis) and increased baroreflex sensitivity (†P < 0.05). In contrast, PVN nNOS inhibition blocked/attenuated these effects in addition to significantly increase in resting MAP and HR (with larger effects in T and l-arginine treated rats vs. respective controls, †P < 0.05). T increased nNOS gene and protein expression within the ventromedial and posterior PVN nuclei (†P < 0.05). PVN nitirite levels were also increased in T and l-arginine groups (†P < 0.05). Data strongly suggest that training by increasing NO availability within PVN preautonomic nuclei favors both the slow down of sympathetic and the augmentation of parasympathetic activity and facilitates baroreflex control, therefore improving autonomic regulation of the heart in healthy rats.

L-arginine Attenuates Hypobaric Hypoxia-Induced Increase in Ornithine Decarboxylase 1

Chronic hypoxia-induced pulmonaryhypertension and vascular remodeling have been shown to be associated with ornithine decarboxylase 1 (ODC1). However, few animal studies have investigated the role of ODC1 in acute hypoxia. We investigated ODC1 gene expression, morphologic and functional changes, and the effect of L-arginine as an attenuator in lung tissues of rats exposed to acute hypobaric hypoxia at a simulated altitude of 6000 m. Sprague-Dawley rats exposed to simulated hypobaric hypoxia (6000 m) for 24, 48, or 72 hours were treated with L-arginine(L-arginine group, 20 mg/100 g intraperitoneal; n=15) or untreated (non-L-arginine group, n=15). Control rats (n=5) were maintained at 2260 m in a normal environment for the same amount of time but were treated without L-arginine. The mean pulmonary artery pressure was measured by PowerLab system. The morphologic and immunohistochemical changes in lung tissue were observed under a microscope. The mRNA and protein levels of ODC1 were measured by real-time polymerase chain reaction and Western-blot, respectively. Hypobaric hypoxia induced pulmonary interstitial hyperemia and capillary expansion in the lungs of rats exposed to acute hypoxia at 6000 m. The mean pulmonary artery pressure and the mRNA and protein levels of ODC1 were significantly increased, which could be attenuated by treatment with L-arginine. L-arginine attenuates acute hypobaric hypoxia-induced increase in mean pulmonary artery pressure and ODC1 gene expression in lung tissues of rats. ODC1 gene contributes to the development of hypoxic pulmonary hypertension.

L-arginine supplementation and risk factors of cardiovascular diseases in healthy men: a double-blind randomized clinical trial

Context: The effect of L-arginine on risk factors of cardiovascular diseases (CVD) has mostly focused on western countries. Since cardiovascular diseases is the second cause of death in Iran and, as far as we are aware, there have been no studies about the effect of L-arginine on CVD risk factors, the aim of this trial was to assess the effects of L-arginine supplementation on CVD risk factors in healthy men. Objective: The purpose of this study was to evaluate the effect of low-dose L-arginine supplementation on CVD risk factors (lipid profile, blood sugar and blood pressure) in Iranian healthy men. Design, setting, participants: We conducted a double-blind randomized controlled trial in 56 patients selected from sport clubs at the Isfahan University of Medical Science between November 2013 and December 2013. Interventions: Healthy men received L-arginine supplementation (2000 mg daily) in the intervention group or placebo (2000 mg maltodextrin daily) in the control group for 45 days. Main outcome measure: The primary outcome measures were we measured the levels of fasting blood sugar, blood pressure and lipid profile including triglyceride (TG), cholesterol, LDL and HDL in healthy subjects. It was hypothesized that these measures would be significantly improved in those receiving L–arginine supplementation. at the beginning and end of the study. Results: In this trial, we had complete data for 52 healthy participants with mean age of 20.85±4.29 years. At the end of study, fasting blood sugar (P=0.001) and lipid profile (triglycerideTG (P&lt;0.001), cholesterol (P&lt;0.001), LDL (P=0.04), HDL (P=0.015)) decreased in the L-arginine group but we found no significant change in the placebo group. In addition, the reduction of fasting blood sugar and lipid profile in L-arginine was significant compared with placebo group. No significant changes were found about systolic (P=0.81) and diastolic blood pressure either in L-arginine or placebo group. (P=0.532). Conclusion: The use of L-arginine significantly improved outcomes compared to placebo.

ЕФЕКТ НАНОЧАСТИНОК ЗАЛІЗА НА ООЦИТИ І КЛІТИНИ ЇХ ФОЛІКУЛЯРНОГО ОТОЧЕННЯ ЗА УМОВ ЕКСПЕРИМЕНТАЛЬНОГО ІМУНОКОМПЛЕКСНОГО УШКОДЖЕННЯ

Новітнім напрямком нанофармакології є використання нанопрепаратів як субстанції для нових лікарських засобів. Перспективними в цьому аспекті є наночастинки металів, зокрема наночастинки нульвалентного заліза (НЧНЗ). Проте можливі механізми протективної або токсичної дії НЧНЗ досліджені недостатньо.Мета роботи – дослідити мейотичне дозрівання ооцитів (МДО), життєздатність клітин фолікулярного оточення ооцитів (ФОО) та перерозподіл однониткових розривів ДНК їх ядер у мишей за умов експериментального імунокомплексного ушкодження та введення блокатора iNOS (аміногуанідін), донора NO (L-аргінін), НЧНЗ.Введення НЧНЗ призводить до пригнічення МДО на стадії Метафаза ІІ і не викликає вірогідних змін параметрів життєздатності клітин ФОО, а також спостерігається деякий перерозподіл ДНК-комет 0/1-х і 2-х у бік останніх по відношенню до величин в контролі. За умов ЕІУ введення L-аргініну і НЧНЗ зумовлює: 1) покращення параметрів МДО на стадії Метафаза І по відношенню до відповідних величин за умов імунізації БСА та введення L-аргініну, проте пригнічення залишається вірогідним по відношенню до відповідних величин в групі імунізації БСА та введення НЧНЗ; 2) зменшення клітинної загибелі – зростає кількість живих клітин ФОО, зменшується кількість клітин з морфологічними ознаками некрозу, порівняно з величинами за умов імунізації та введення L-аргініну; 3) по відношенню до величин групи імунізації і введення L-аргініну спостерігається перерозподіл однониткових розривів ядер 2-х і 3-х класу у бік останніх, однак по відношенню до величин групи імунізації і введення НЧНЗ перерозподіл відбувається між ядрами 0-х/1-х і 3-х у бік збільшення останніх. Вперше показано, що NO бере участь в ефекті НЧНЗ на ооцити і клітини ФОО при розвитку експериментального імунокомплексного ушкодження.

Effects of L‐arginine Supplementation on the Tissue Production of Nitric Oxide and Cardiovascular Modulation by the Paraventricular Nucleus of Hypothalamus

L‐Arginine is the substrate for nitric oxide (NO) synthesis and in the paraventricular nucleus of the hypothalamus (PVN) NO plays an important role in cardiovascular function. The objective of this study was to evaluate the effects of L‐arginine supplementation on cardiovascular responses by PVN and NO production. Wistar rats were used (220–250g) randomly divided into two groups: control (C) or L‐arginine (LA). The supplementation with L‐arginine was conducted in the LA group (62.5 mg/mL/rat/day), by oral gavage, and Group C received water (1 mL) for 4 weeks, 5times/week. Then the animals underwent to guide cannulas implantation to the PVN and artery and femoral vein catheterization. The baseline parameters of mean arterial pressure (MAP) and heart rate (HR) were recorded 24 hours after catheterization and held bilateral administration of 0.9% saline or an nNOS inhibitor (n‐Propyl‐L‐Arginine, 4nmol/100NL) in the PVN. We collected heart, kidneys, thoracic aorta, and punchs of the PVN for nitrite dosages by Cadmium‐Griess method. Spectral analysis was performed by the software Cardio Series (version 2.4). The supplementation with L‐arginine caused resting bradycardia (C: 359 ± 6 vs. LA: 335 ± 6 b/min) without change in MAP, as well as greater pressor response (ΔPAM: C: 17 ± 2 vs. LA: 26 ± 3 mmHg) and tachycardia (ΔFC: C: 86 ± 6 vs. LA: 129 ± 13 b/min) to n‐propyl in the PVN. At baseline the spectral analysis of rats of LA group showed: lower sympathetic modulation for systolic blood pressure (LF: C: 4.6 ± 0.6 vs. LA: 2.1 ± 0.4 mmHg2) smaller variance in pulse interval (C: 42.4 ± 3.2 vs. LA: 24.6 ± 5.1 ms2), lower sympathovagal index (LF/HF: C: 0.8 ± 0.1 vs. LA: 0.3 ± 12:07) and increase of spontaneous baroreflex gain: (Gain full baroreflex: C: 1.3 ± 0.1 vs. LA: 2.2 ± 0.2 ms/mm Hg; Gain Up: C: 1.4 ± 0.1 vs. LA: 2.5 ± 0.3 ms/mm Hg; Gain Down: C: 1.2 ± 0.1 vs. LA: 1.8 ± 0.2 ms/mmHg). In addition, LA animals showed higher concentrations of nitrite in the PVN (C: 3.3 ± 0.7 vs. LA: 5.5 ± 0.7 uM/mg/PVN), kidneys (C: 7 ± 1 vs. LA: 18 ± 3 uM) and thoracic aorta (C: 4 ± 0.6; LA: 12 ± 3 .mu.M). Therefore, supplementation with L‐arginine modified the baseline autonomic control, increase in nitregirc tonus by NO in the PVN via nNOS, and an increase in NO bioavailability, leading to similar effects obtain after exercise training.Support or Funding InformationCNPq (fellowship program)