Effects Of Dietary L-arginine Supplementation Research Articles

Arginine supplementation in the feed of gestating sows

The high prolificacy achieved by the genetic improvement of sows has resulted in decreased birth weights and uniformity of litters, as well as increased prenatal and preweaning mortality. Amino acids, such as arginine, are essential for the proper development of the placenta and the swine fetus. Their role include regulating angiogenesis, vascular development, and therefore potentially placental vascularization, providing a greater supply of nutrients and oxygen from the sow to the fetuses. The objective of the trial was to evaluate the effects of dietary l-arginine supplementation on the reproductive and productive performance of gestating sows from days 30 to 60 and days 80 to 114 of gestation. Forty-eight pluriparous sows with two to six parities were divided into two different treatments with a total of 24 replicates per treatment. The treatments consisted of a control diet without l-arginine supplementation (CON) and a diet with top-dressed supplementation of 1.0% l-arginine (ARG). Blood samples were collected from the sows on days 30, 60, 90, and 114 of gestation to determine the plasma concentrations of albumin, creatinine, and urea. Sows were weighed 24 h after farrowing and at weaning to calculate body weight loss during lactation. Piglets were individually weighed at birth before the first feeding and at weaning. Supplementation of the diet with l-arginine during gestation affected (p = 0.025) the plasma concentrations of triglycerides at 60 days, but it did not impact the albumin, creatinine, and urea's concentrations at 30, 60, 90, and 114 days of gestation. However, the concentrations of creatinine differed (p = 0.006) for gestational periods. The average weight of piglets born alive was greater (p = 0.0485) for ARG compared to CON and the other performance and reproductive characteristics did not differ. The percentage of piglets born weighing over 1.81 kg was greater (p < 0.05) for sows fed ARG than in CON fed sows. l-arginine supplementation in the feed of gestating sows increased the average weight of piglets born alive and the percentage of piglets with a birth weight above 1.81 kg, reduced the concentration of triglycerides at 60 days of gestation, and the gestational period had effect about the creatinine concentrations.

L-arginine supplementation during the final third of gestation improves litter uniformity and physical characteristics of neonatal piglet thermoregulation.

The study assessed the effects of dietary L-arginine supplementation from days 85 to 115 of gestation on sow performance, litter quality, piglet physiology and survival variables in the first 24hr of life. Twenty multiparous sows, with a history of hyperprolificacy (more than 14 piglets per litter), were used. A completely randomized experimental design was used, consisting of two treatments: feed supplemented or not with 1% L-arginine from days 85 to 115 of gestation. The experimental unit consisted of the sow and its respective litter, using 10 replicates per treatment. The sows were distributed into the treatments based on body condition and parity. Supplementation with L-arginine reduced the within-litter standard deviation and the within-litter coefficient of variation of piglet weight at 24hr by 54g and 4.14 percentage points respectively (p=.029; p=.035). Supplementation with 1.0% L-arginine decreased the percentages of piglets weighing less than 800g by 5.60 and 5.08 points at birth and at 24hr of life respectively. Piglets from sows supplemented with L-arginine had higher (p=.088) average rectal temperatures at birth and lower (p=.030) rectal temperature at 24hr of life in comparison with control piglets. No significant differences in placental weight or estimated colostrum production and intake were observed in the first 24hr of life. At 24hr of life, piglets weighing less than 1,000g and from supplemented sows had lower (p=.048) surface/mass ratios and higher body mass index (p=.070). Piglets from supplemented sows and who weighed 1601 to 1,800g had lower body mass index and ponderal index (p=.002; p=.003). Supplementation with L-arginine during the final third of gestation reduces the incidence of unviable piglets (<800g) and improved litter uniformity and piglets' body conformation within the first 24hr of life.

Effects of Dietary L-arginine Supplementation from Conception to Post- Weaning in Piglets.

Weaned piglets experience sudden changes in their dietary patterns such as withdrawal from the easily digestible watery milk to a coarse cereal diet with both systemic and intestinal disruptions coupling with the expression of pro-inflammatory proteins which affects the immune system and the concentrations of haptoglobin including both positive and negative acute-phase proteins in the plasma. L-arginine is an important protein amino acid for piglets, but its inadequate synthesis is a nutritional problem for both sows and piglets. Recent studies indicated that dietary supplementation of L-arginine increased feed intake, uterine growth, placental growth and nutrient transport, maternal growth and health, embryonic survival, piglets birth weight, piglet's growth, and productivity, and decreased stillbirths. L-arginine is essential in several important pathways involved in the growth and development of piglets such as nitric oxide synthesis, energy metabolism, polyamine synthesis, cellular protein production and muscle accretion, and the synthesis of other functional amino acids. However, the underlying molecular mechanism in these key pathways remains largely unresolved. This review was conducted on the general hypothesis that L-arginine increased the growth and survival of post-weaning piglets. We discussed the effects of dietary L-arginine supplementation during gestation, parturition, lactation, weaning, and post-weaning in pigs as each of these stages influences the health and survival of sows and their progenies. Therefore, the aim of this review was to discuss through a logical approach the effects of L-arginine supplementation on piglet's growth and survival from conception to postweaning.

Effects of dietary l-arginine on growth performance, nutrient digestibility, gas emission, and meat quality in finishing pigs

This study was conducted to evaluate the effects of dietary l-arginine supplementation on growth performance, nutrient digestibility, gas emission and meat quality. A total of 120 crossbred [(Landrace × Yorkshire) × Duroc] pigs with an average initial body weight (BW) of 53.80 ± 1.86 kg were used in this 10-week feeding trial. The pigs were randomly allotted to 1 of 3 dietary treatments (5 pigs/pen and 8 replicates/treatment) in a randomized complete block design according to their sex (2 gilts and 3 barrows) and BW. Dietary treatments included: 1) CON (basal diet); 2) LA0.5 (CON + 0.5 g/kg l-arginine); 3) LA1.0 (CON + 1.0 g/kg l-arginine). The result showed that l-arginine did not affect pig growth performance, nutrient digestibility, or gas emission. However, dietary l-arginine supplementation linearly increased (P < 0.05) muscle marbling score, while linearly decreasing (P < 0.05) cooking loss and drip loss of pork muscle. Collectively, results of current study indicate that supplementation with 1.0 g/kg l-arginine improved meat quality without any significant effect on growth performance in finishing pigs.

Effects of dietary L-arginine supplementation to early pregnant mares on conceptus diameter-Preliminary findings.

ContentsThe importance of the amino acid L‐arginine (ARG) for conceptus growth and litter size has been demonstrated in various species. L‐arginine is part of embryo‐derived polyamines, a substrate for nitric oxide synthase and stimulates protein synthesis by the embryo. In the present study, we have investigated whether dietary L‐arginine supplementation stimulates early conceptus growth in mares. Warmblood mares with singleton pregnancies received either an arginine‐supplemented diet (approximately 0.0125% of body weight, n = 12) or a control diet (n = 11) from days 15 to 45 after ovulation. Diameter of the embryonic vesicle (days 14, 17, 20 of pregnancy) and size of the embryo respective foetus (length and maximal diameter, days 25–45 of pregnancy at 5‐day intervals) were determined by transrectal ultrasound. At foaling, weight and size of the foal and the placenta were determined. Blood for determination of equine chorionic gonadotrophin (eCG) and progestin concentrations was collected repeatedly. Neither eCG nor progestin concentration in plasma of mares differed between groups at any time. No effects of arginine treatment on diameter of the embryonic vesicle between days 14 and 20 of pregnancy were detected. Diameter of the embryo/foetus on days 40 to 45 of pregnancy strongly tended to be enhanced by arginine supplementation (p = 0.06). Weight and size of neither the foal nor placenta at birth differed between groups. In conclusion, L‐arginine supplementation was without negative effects on early equine embryos and may support embryonic growth at the beginning of placentation.

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.

Novel metabolic roles of L-arginine in body energy metabolism and possible clinical applications.

Although the body can synthesize L-arginine, exogenous supplementation may be sometimes necessary, especially in particular conditions which results in depleted endogenous source. Among diseases and states when exogenous supplementation may be necessary are: burns, severe wounds, infections, insufficient circulation, intensive physical activity or sterility. In recent time, the attention was paid to the use of L-arginine supplementation by athletes during intensive sport activity, to enhance tissue growth and general performance, to potentiate the ergogenic potential and muscle tolerance to high intensive work and gas exchange threshold, to decrease ammonia liberation and recovery performance period and to improve wound healing. High-intensity exercise produces transient hyperammoniemia, presumably due to AMP catabolism. Catabolic pathways of AMP may involve its deamination or dephosphorylation, mainly in order to compensate fall in adenylate enrgy charge (AEC), due to AMP rise. The enzymes of purine metabolism have been documented to be particularly sensitive to the effect of dietary L-arginine supplementation. L-arginine supplementation leads to redirection of AMP deamination on account of increased AMP dephosphorylation and subsequent adenosine production and may increase ATP regeneration via activation of AMP kinase (AMPK) pathway. The central role of AMPK in regulating cellular ATP regeneration, makes this enzyme as a central control point in energy homeostasis. The effects of L-arginine supplementation on energy expenditure were successful independently of age or previous disease, in young sport active, elderly, older population and patients with angina pectoris.

Dietary supplementation with l-arginine between days 14 and 25 of gestation enhances embryonic development and survival in gilts

Embryonic loss is a major problem in mammals, but there are few effective ways to prevent it. Using a porcine model, we determined effects of dietary L-arginine supplementation between days 14 and 25 of gestation on embryonic growth and survival. Gilts were checked daily for estrus with boars in the morning and bred at onset of the second estrus and 12 h later (the time of breeding = day 0 of gestation). Between days 14 and 25 of gestation, 15 gilts/treatment were housed individually and fed twice daily 1 kg of a corn- and soybean meal-based diet supplemented with 0.0, 0.4, or 0.8 % L-arginine. All diets were made isonitrogenous by addition of L-alanine. On day 25 of gestation, gilts were hysterectomized to obtain conceptuses. Compared with controls, dietary supplementation with 0.4 or 0.8 % L-arginine increased (P ≤ 0.05) arginine concentrations in maternal plasma, total volume of amniotic fluid; total amounts of arginine in allantoic and amniotic fluids; total amounts of fructose and most amino acids in amniotic fluid; placental growth; and the number of viable fetuses per litter by 2. The numbers of total fetuses, fetal weight, corpora lutea, volume of allantoic fluid, maternal circulating levels of progesterone and estrogen, or total amounts of hormones in allantoic fluid did not differ among the three treatment groups. Reproductive performance of gilts did not differ between the 0.4 and 0.8 % L-arginine groups. Thus, dietary supplementation with 0.4 or 0.8 % L-arginine between days 14 and 25 of gestation enhances embryonic/fetal survival in swine.

Dietary L-Arginine Supplementation during Gestation in Mice Enhances Reproductive Performance andVegfr2Transcription Activity in the Fetoplacental Unit 3

Regarded as one of the most versatile amino acids, arginine serves as a precursor for many molecules and has been reported to improve the reproductive performance of rats and pigs. To this end, we sought to determine if dietary L-arginine alters fetoplacental vascular endothelial growth factor receptor-2 (Vegfr2) transcription activity. Eighteen wild-type FVB/N female mice were bred to homozygous FVB/N-Tg(Vegfr2-luc)-Xen male mice. Bred female mice received 1 of 2 experimental diets: one supplemented with 2.00% (wt:wt) L-arginine (+Arg) or 1 supplemented with 4.10% (wt:wt) alanine (+Ala) to serve as an isonitrogenous control for +Arg. In addition, 6 mice were fed a nonsupplemented control (Con) diet to normalize bioluminescent imaging data. All data were analyzed using ANOVA followed by Fisher’s least significant difference. Total feed intake did not differ between groups; however, mice in the +Arg group consumed more arginine (P <0.05). Arginine supplementation increased weight gain during the latter one-third of gestation (d 12– 18), total litter size, number of pups born alive, number of placental attachment sites, litter birth weight, and litter weight of pups born alive but decreased the individual birth weights (P <0.05). During d 12–18, arginine supplementation increased (P <0.05) the mean totalVegfr2transcription activity andVegfr2transcription activity corrected for fetoplacental mass. Moreover, mice in the +Arg group had an earlier rise inVegfr2transcription activity. In conclusion, our results demonstrate that the beneficial effect of dietary L-arginine supplementation on mammalian reproduction is associated with enhancedVegfr2transcription activity in fetoplacental tissues.

English

This study aimed to investigate the effects of dietary L-arginine supplementation on the intestinal development of neonatal piglets and the underlying mechanisms.&nbsp;36neonatal piglets were randomly allocated into three diet groups: control group (supplemented with 0% L-arginine), 0.4 and 0.8% L-arginine groups. When compared with the control, dietary supplementation with L-arginine decreased (P&lt;0.05) blood urea nitrogen (BUN), and improved (P&lt;0.05) serum T3 and insulin level of the piglets on day 11. Arginine and its metabolites (citrulline and ornithine) were elevated, additionally, dietary supplementation with 0.8% L-arginine markedly enhanced&nbsp;jejunal villus height, villus area on day 11 and D-xylose absorption rate on day 19.&nbsp;Dietary supplementation with 0.8% L-arginine increased (P&lt;0.05) activities of maltose and lactose on day 18, respectively. This effect correlated with profound change in enzyme activities as inducible nitric oxide synthetase (iNOS), glutamine synthetase (GS) and ornithine decarboxylase (ODC) were elevated on day 18. The concentrations of spermine was increased (P&lt;0.05) by L-arginine supplementation on day 18. These results collectively suggest that dietary L-arginine supplementation improves protein synthesis and intestinal development of the neonatal pigs, the underlying mechanism includes dietary L-arginine supplementation which regulated the productions of intestinal polyamine in jejunum, and stimulated endogenous arginine-synthesizing enzymes in neonatal piglets. &nbsp; Key words:&nbsp;Neonatal pig, L-arginine, intestinal development, arginine-synthetases. &nbsp; &nbsp

Effect of Dietary L-Arginine Supplementation on Fetoplacental Vegfr2 Gene Activity and Reproductive Performance in a Bioluminescent Murine Pregnancy Model.

Arginine is a conditionally essential amino acid for mature mammals, yet it is considered to be essential for young, developing mammals. Regarded as one of the most versatile amino acids, arginine serves as a precursor for many molecules and has been reported to improve the reproductive performance of rats and pigs. While the mechanism is still unclear, arginine has been proposed to alter angiogenesis during pregnancy. To this end, the objective of this study was to determine whether the beneficial effect that dietary arginine supplementation has on reproductive performance is associated with an alteration of fetoplacental vascular endothelial growth factor receptor-2 (Vegfr2) transcription activity. Homozygous FVB/N-Tg(Vegfr2-luc)-Xen transgenic male mice (Vegf2-luc), genetically modified with a cloned murine Vegfr2 promoter upstream to firefly luciferase, were purchased from Caliper Life Sciences, Inc. (Hopkinton, MA, USA). Eighteen wild-type FVB/N females were bred to Vegfr2-luc males so that only the fetoplacental tissues would possess the Vegfr2-luc transgene. Once bred, females (n=6 per diet) received a control diet (Con) or the diet supplemented with either 2.0% (wt:wt) L-arginine (+Arg), or 4.1% (wt:wt) alanine (+Ala) which served as an isonitrogenous control for the +Arg diet. Body weight and total feed intake were recorded during gestation. Pregnant mice were imaged daily from day 12 to day 18 of gestation to detect luciferase activity as an indicator of Vegfr2 gene expression using the IVIS 100 imaging system (Caliper Life Sciences, Inc.). Number of pups and litter weight were recorded at birth, and the number of placental attachments was determined three weeks postpartum. All data were analyzed using ANOVA followed by Fisher's LSD test for pairwise comparison. The threshold of significance was fixed at P ≤ 0.05 and a tendency at P ≤ 0.10. Total feed intake did not differ significantly between groups; however, animals in the +Arg group consumed more arginine than others (P < 0.05). Arginine supplementation increased weight gain during the latter third of gestation (day 12 to day 18), total litter size, number of pups born alive, number of placental attachment sites, litter birth weight, and litter weight of pups born alive (P < 0.05). Conversely, individual birth weights of pups born alive was less (P < 0.05) in those born to arginine supplemented dams. There was a tendency (P = 0.07) for average total fetoplacental Vegfr2 gene activity to differ between groups, and this effect was significantly greater in the arginine supplemented animals when compared to the animals receiving the isonitrogenous alanine supplemented diet (P < 0.05). When corrected for fetoplacental mass, Vegfr2 gene activity did not significantly differ between groups; however, animals supplemented with arginine displayed an earlier rise in Vegfr2 gene activity. In conclusion, our results demonstrate that the beneficial effect of dietary arginine supplementation on mammalian reproduction is associated with an earlier increase in Vegfr2 transcription activity in fetoplacental tissues. This research was supported by the USDA-ARS Biophotonics Initiative #58-6402-3-0120. (platform)

Effects of dietary l-arginine supplementation to gilts during early gestation on foetal survival, growth and myofiber formation

The effects of l-arginine on porcine foetal development and myogenesis were determined. Twenty Swiss Large White gilts were randomly allocated to either the control (C) or l-arginine treatment (A). In addition to the standard gestation diet, A-sows received 26 g l-arginine daily from days 14 to 28 of gestation. At day 75 of pregnancy, sows were sacrificed and the number and weight of foetuses were recorded. From each litter, the lightest, heaviest and the ones with an average foetal weight (FtW) were selected. Primary (P), secondary (S) and total myofiber number as well as S/P ratio were determined in the semitendinosus (ST) and rhomboideus (RH) muscles. In A-sows, the number of viable foetuses (13.0 v. 9.3) and total FtW (4925 v. 3729 g) was greater (P ⩽ 0.04) than in C-sows. Compared to C-sow foetuses, the ST of A-sow foetuses had 7% more (17 699 v. 16 477; P = 0.04) P myofibers and the S/P ratio in both muscles was lower (ST = 20.3 v. 21.5; RH = 24.1 v. 27.1; P ⩽ 0.07). Regardless of the maternal diet, the S myofiber number and the S/P ratio in both muscles were greater (P ⩽ 0.01) in foetuses with a high FtW compared to low FtW. These data suggest that l-arginine supplemented to gilts during early gestation enhanced foetal survival and in the ST positively affected the primary phase of myofiber formation.

L-Arginine promotes angiogenesis in the chronically hypoxic lung: a novel mechanism ameliorating pulmonary hypertension

Chronic alveolar hypoxia, whether due to residence at high altitude or lung disease, leads to a sustained increase in pulmonary vascular resistance and pulmonary hypertension (PH). Strategies that augment endogenous nitric oxide production or activity, including l-arginine supplementation, attenuate the development of PH. This action has been attributed to inhibition of vessel wall remodeling, thus preventing structural narrowing of the vascular lumen. However, more recent evidence suggests that structural changes are not responsible for the elevated vascular resistance observed in chronic hypoxic PH, calling into question the previous explanation for the action of l-arginine. We examined the effect of dietary l-arginine supplementation on pulmonary vasoconstriction, structurally determined maximum vascular lumen diameter, and vessel length in rats during 2 wk of exposure to hypoxia. l-Arginine attenuated the development of hypoxic PH by preventing increased arteriolar resistance. It did not alter mean maximal vascular lumen diameter, nor did it augment nitric oxide-mediated vasodilatation, in chronically hypoxic lungs. However, the total length of vessels within the gas exchange region of the hypoxic lungs was significantly increased after l-arginine supplementation. These findings suggest that dietary l-arginine ameliorated hypoxic PH, but not by an effect on the structurally determined lumen diameter of pulmonary blood vessels. l-Arginine enhanced angiogenesis in the hypoxic pulmonary circulation, which may attenuate hypoxic PH by producing new parallel vascular pathways through the lung.

Dietary L‐arginine supplementation affects immune status of pregnant gilts

This study was conducted to determine the effect of dietary L-arginine supplementation on the immune status of pregnant gilts. A total of 53 pregnant gilts with an initial body weight of 166.25+1.81 kg and backfat thickness of 13.26+0.21 mm were housed individually in gestation crates. At d 30 of gestation, gilts were assigned randomly to corn- and soybean-based diets supplemented with 1.0 % L-arginine (treatment group) or 1.7 % L-alanine (isonitrogenous control). Both diets contained 3.1 Mcal ME/kg and 12.2% CP. Gilts were fed 1 kg of the diet twice a day at 0700 and at 1700 h during the gestation period. Blood samples were collected at 0900 on d 30, 50, 70, 90 and 110 d of gestation. Whole blood samples were used for hematological analysis as determined by CELL-DYN®. The numbers of white blood cells, neutrophil, basophil, eosinophil, monocytes, and total lymphocytes did not differ (P>0.05) between the control and treatment groups at d 30, 50, 70, and 90 of gestation. However, compared with the control group, arginine supplementation increased the numbers of white blood cell (P=0.013), neutrophil (P=0.007) and basophil (P=0.011) at 110 d of gestation. These results demonstrate the L-arginine supplementation at 1% affects immune cell populations of first parity sows. Supported by Texas Tech Univ., Texas A&M Univ., Ajinomoto Co., and USDA-NRI.

L-Arginine Supplementation Causes Additional Effects on Exercise-Induced Angiogenesis and VEGF Expression in the Heart and Hind-Leg Muscles of Middle-Aged Rats

The effects of dietary L-arginine supplementation on exercise-induced angiogenesis and VEGF expression were examined in male middle-aged (12 months old) Wistar rats. Exercise training lasted for six weeks at 20 m/min on a 0% gradient for 10-60 min/day. Rats in the L-arginine-treated groups drank water containing 2.5% L-arginine. According to histochemical identification of the capillary profile, in the soleus muscle the capillary-to-fiber (C:F) ratio showed a significantly greater value in the L-arginine-treated training group than in both the sedentary control and training groups. Training with L-arginine significantly increased the C:F ratio in the subendocardium of the left ventricle, whereas training alone did not. In the plantaris muscle, training with or without L-arginine significantly increased the capillary density, but it did not affect the C:F ratio. A Western blot analysis showed that training with L-arginine significantly increased VEGF protein expression by 2.9-fold in the soleus muscle and by 1.7-fold in the left ventricle, but the increase with training alone was insignificant. The tissue endothelial nitric oxide synthase protein levels were significantly increased in both the soleus (by 1.3-fold) and the left ventricle (by 1.4-fold) only after training with L-arginine supplementation. In the plantaris muscle, these protein levels did not change after either training or L-arginine treatment. The present results suggest that in middle-aged rats, L-arginine administration caused additional effects on exercise-induced angiogenesis by presumably promoting VEGF expression in the hind-leg muscle as well as in the left ventricle.

Effects of dietary L-arginine supplementation on serum lipids and intestinal enzyme activities in diabetic rats.

We investigated whether dietary supplementation with L-arginine, the endogenous precursor of nitric oxide, might affect serum lipid levels and activities of intestinal mucosa enzymes in animals, in which diabetes was induced by administration of streptozotocin. Control and diabetic rats were fed diets with or without 2% L-arginine supplementation for 4 weeks. Diabetic rats had significantly higher concentrations of serum triglycerides and LDL-cholesterol than control rats. These alterations were partially reduced by L-arginine supplementation. Experimental diabetes did not influence the lactase and leucine aminopeptidase activity in the intestine, but the activity of alkaline phosphatase was increased. Furthermore, activities of maltase and sucrase in the intestinal mucosa were elevated in streptozotocin-induced diabetic rats and were restored to control levels after dietary L-arginine supplementation. On the basis of the present experimental evidence, dietary L-arginine supplementation appears to affect the metabolism of lipoproteins and might alleviate some gastrointestinal dysfunctions, commonly seen in diabetes mellitus.

No effect of an L-arginine-enriched medical food (HeartBars) on endothelial function and platelet aggregation in subjects with hypercholesterolemia

Background Providing l-arginine as a precursor for nitric oxide has been proposed to improve endothelial function in populations at high risk for cardiovascular events. We studied the effects of dietary l-arginine supplementation with HeartBars (a medical food rich in L-arginine, Cooke Pharma, Belmont, Calif) on flow-mediated dilation and markers of endothelial function in subjects with hypercholesterolemia. Methods We randomly assigned 47 subjects with hypercholesterolemia to receive one HeartBar containing 3.3 g l-arginine each, or a placebo bar, consumed twice daily for 2 weeks. Flow-mediated dilation, platelet aggregation studies, and soluble levels of endothelial and platelet adhesion molecules were obtained before and after the 2-week treatment period. Results Baseline and follow-up levels of l-arginine were 78.5 ± 28.2 μmol/L and 80.7 ± 26.7 μmol/L, respectively ( P = .54). The HeartBar group had no improvement in flow-mediated dilation; changes in brachial artery diameter at baseline and follow-up were 5.52% ± 3.32% and 4.96% ± 2.39%, respectively. There were also no changes in the soluble levels of E-selectin and P-selectin by treatment group. Conclusions In our study, 2 weeks of HeartBar supplementation in subjects with hypercholesterolemia showed no favorable effects on endothelial or platelet function. (Am Heart J 2003;145:e15.)

Protective effects of dietary L-arginine supplementation on chronic cyclosporine nephrotoxicity.

L-Arginine (L-Arg), the substrate for nitric oxide (NO) synthase producing NO, and the NO synthase inhibitor, N-nitro-L-arginine-methyl ester (L-NAME), have both been shown to modify acute cyclosporine (CsA)-induced intrarenal vasoconstriction. However, the mechanism of chronic CsA nephrotoxicity characterized by progressive tubulointerstitial fibrosis (TIF) remains unclear. Thus, we examined the pathogenetic role of NO in a rat model of chronic CsA nephropathy. Rats were given vehicle, CsA (7.5 mg/kg), CsA + L-Arg (1.7 g/kg), CsA + D-arginine (1.7 g/kg), and CsA + L-NAME (3.5 mg/kg) for 28 days on a low-salt diet. NO production, glomerular filtration rate (GFR), blood and urine chemistry, and histology were assessed. L-Arg treatment significantly enhanced NO biosynthesis and protected animals from impaired GFR and development of TIF induced by CsA, whereas D-arginine did not. In contrast, L-NAME strikingly reduced urinary NO and worsened both GFR and TIF compared to the CsA alone group, whereas L-NAME did not change renal function and histology in the vehicle group. Chronic CsA nephrotoxicity can be aggravated by NO blockade and ameliorated by NO enhancement, suggesting that NO has an important role in the mechanism of chronic CsA nephropathy.

Regional Blood Flow in Dahl-Iwai Salt Sensitive Rats and the Effects of Dietary L-arginine Supplementation

Regional Blood Flow in Dahl-Iwai Salt Sensitive Rats and the Effects of Dietary L-arginine Supplementation