Clinical Studies
References
L-Arginine is an essential amino acid with anabolic and immune system supportive effects. It is required for growth, immune function, wound healing and many aspects of protein metabolism. Arginine is necessary for the production of growth hormone. It is also a precursor for nitric oxide, a critical substance that helps regulate the function of cardiovascular, nervous and immune systems and which is essential for muscle growth.
L-Arginine may be helpful in cardiovascular conditions including congestive heart failure (CHF), angina pectoris, hypertension and coronary artery disease. It may also be helpful for intermittent claudication, senile dementia, erectile dysfunction, male infertility, prevention of the common cold, interstitial cystitis, improving athletic performance, for migraine headaches and as an adjunct to chemotherapy in breast cancer. After surgery it may be helpful in reducing infections, improve wound healing and shorten recovery time.
Published Clinical Studiesclin
L-Arginine HCL
Department of Surgery, Yale University School of Medicine, New Haven, Connecticut 06520-8041, USA.
PURPOSE: Nitric oxide synthase activity is decreased in the urine of patients with interstitial cystitis compared to the urine of controls. In a preliminary trial oral L-arginine, the substrate for nitric oxide synthase, increased urinary nitric oxide synthase activity and improved interstitial cystitis symptoms. This randomized, double-blind, placebo controlled study further investigates the efficacy of L-arginine treatment for interstitial cystitis. MATERIALS AND METHODS: A total of 53 interstitial cystitis patients were assigned to receive daily 1,500 mg. L-arginine or placebo orally for 3 months. Interstitial cystitis symptoms were assessed by interviews at 2 weeks, and 1, 2 and 3 months. RESULTS: The trial was completed by 21 of 27 patients in the L-arginine group and 25 of 26 in the placebo group. Using per protocol analysis 29% (6 of 21 patients) in the L-arginine group and 8% (2 of 25) in the placebo group were clinically improved by the end of the trial (p = 0.07). A Likert scale showed greater global improvement in the L-arginine group (48%, 10 of 21) compared to the placebo group (24%, 6 of 25) at 3 months (p = 0.05) with a decrease in pain intensity (p = 0.04), and tendency toward improvement in urgency (p = 0.06) and frequency of pain (p = 0.09). Using an intention to treat approach to analysis there were no differences between groups. CONCLUSIONS: Oral L-arginine (1,500 mg. daily) may decrease pain and urgency in a subset of interstitial cystitis patients.
Publication Types:
PMID: 9915448 [PubMed - indexed for MEDLINE]
L-arginine improves endothelial vasoreactivity and reduces thrombogenicity after thrombolysis in experimental deep venous thrombosis.
Lin PH, Johnson CK, Pullium JK, Bush RL, Conklin BS, Chen C, Lumsden AB.
Division of Vascular Surgery and Endovascular Therapy, DeBakey Department of Surgery, Baylor College of Medicine, Houston VAMC (112), 2002 Holcomb Boulevard, Houston, TX 77030, USA. plin@bcm.tmc.edu
PURPOSE: Nitric oxide (NO) is important in regulation of platelet aggregation, endothelial function, and intravascular thrombosis. The purposes of this study were to assess the effect of thrombolysis on endothelial function in a porcine model of deep venous thrombosis (DVT) and to evaluate the effect of NO precursor l-arginine on endothelial function after thrombolytic therapy. METHODS: DVT was created in bilateral iliac veins by deploying a self-expanding stent-graft that incorporated an intraluminal stenosis, from a groin approach. Five pigs underwent sham operation. After 7 days of DVT, animals were randomized to three groups: saline pulse-spray (saline group, n = 5), thrombolytic pulse-spray with tissue plasminogen activator (alteplase, 8 mg; t-PA group, n = 5), and thrombolytic pulse-spray plus intravenous l-arginine (20 mmol/L; arginine group, n = 5). At 2 weeks iliac vein patency was evaluated at venography and intravascular ultrasound scanning. NO level was determined with a chemiluminescent assay of the nitrite and nitrate metabolites (NO(x)). Thrombogenicity was evaluated with radiolabeled platelet and fibrin deposition. Veins were harvested and evaluated with light microscopy and scanning electron microscopy. Endothelial function was evaluated with organ chamber analysis. RESULTS: All iliac veins remained patent at 2 weeks. The luminal areas in the sham, saline, t-PA, and arginine groups were 53 +/- 23 mm(2), 14 +/- 11 mm(2), 34 +/- 19 mm(2), and 42 +/- 21 mm(2), respectively. No difference in endothelial cell structure was observed between the three treatment groups at light microscopy or scanning electron microscopy. Although no difference in fibrin deposition was noted among the three treatment groups, decreased platelet deposition occurred in the arginine group compared with the saline or t-PA groups (P <.05). The arginine group showed greater endothelial-dependent relaxation compared with the t-PA or saline groups (73% +/- 23% vs 49% +/- 18% and 32% +/- 21%; P <.05). Local NO(x) level in the arginine group was correspondingly higher compared with the saline or t-PA groups (1.8 +/- 0.3 micromol/L vs 0.3 +/- 0.05 micromol/L and 0.2 +/- 0.04 micromol/L; P <.05). CONCLUSIONS: NO precursor l-arginine supplementation enhances NO production at sites of venous thrombosis. Moreover, l-arginine preserves endothelial vasoreactivity and reduces platelet deposition after thrombolysis in iliac DVT. These data suggest that l-arginine may preserve endothelial function after thrombolysis and may reduce the likelihood of postthrombotic syndrome.
PMID: 14681647 [PubMed - in process]
3
[Effects of L-arginine on the function of platelet aggregation during hepatic ischemia/reperfusion injury]
Wang WT, Lin LN, Pan XR, Xu ZJ.
Department of Pathophysiology, Wenzhou Medical College, Wenzhou 325027, Zhejiang, China.
OBJECTIVE: To explore the effects of L-arginine (L-Arg) on the function of platelet aggregation during hepatic ischemia-reperfusion injury (HIRI). METHODS: The changes in maximum aggregating rate of circulating platelets (Pt(max)), its maximum aggregating time (PtT) as well as its aggregating slopes (PtS) were measured. Effects of L-Arg on those parameters were observed during HIRI in 20 rabbits and 18 patients who were scheduled for elective hepatic surgery. RESULTS: Pt max and PtS all increased significantly (P<0.05 and P<0.01), while PtT decreased remarkably (both P<0.05) during HIRI of rabbits and patients. After treatment with L-Arg, the abnormal changes of parameters as above were all alleviated remarkably (P<0.05 and P<0.01). CONCLUSION: It is indicated that L-Arg can effectively regutate the function of platelet aggregation during HIRI.
PMID: 14706205 [PubMed - in process]
4
Dietary L-Arginine Supplementation Improves the Glomerular Filtration Rate and Renal Blood Flow After 24 Hours of Unilateral Ureteral Obstruction in Rats.
Ito K, Chen J, Vaughan ED Jr, Seshan SV, Poppas DP, Felsen D.
SUMMARY: PURPOSE Unilateral ureteral obstruction (UUO) results in a significant change in renal blood flow (RBF) and glomerular filtration rate (GFR) by 24 hours. The intake of L-arginine, a substrate of nitric oxide (NO) synthase (NOS), can augment NO production. NO can maintain renal function through its vasodilatory action. Therefore, we examined the effect of dietary arginine supplementation on renal function in UUO.MATERIALS AND METHODS GFR and RBF were measured by inulin and para-aminohippurate clearance, respectively, in control rats and in rats 24 hours after UUO. Rats were given arginine with or without the concomitant administration of N-nitro-L-arginine methyl ester. Urinary nitrate/nitrite (NO2/NO3) was measured by the Griess reaction and urinary cyclic guanosine monophosphate was determined by enzyme-linked immunosorbent assay. The expression of renal inducible NOS was determined by immunohistochemistry.RESULTS Urinary NO2/NO3 was significantly increased after 2 weeks of arginine, confirming increased NO production. In control rats GFR and RBF were not significantly different in untreated vs arginine treated groups. In contrast, arginine treatment significantly increased GFR in the obstructed kidney (0.06 +/- 0.01 to 0.14 +/- 0.02 ml per minute per 100 gm) and the contralateral kidney compared with control UUO. RBF was also significantly increased by arginine. The increases in renal function with arginine were blunted by a NOS inhibitor in obstructed and contralateral kidneys. Inducible NOS expression was increased in obstructed and contralateral kidneys.CONCLUSIONS This study demonstrates that L-arginine supplementation can improve renal function in acute UUO. This finding suggests that NO system may be a future site of pharmacological intervention for UUO.
PMID: 14713855 [PubMed - as supplied by publisher]
Nitric oxide synthase, an essential factor in peripheral nerve regeneration.5
Keilhoff G, Fansa H, Wolf G.
Institute of Medical Neurobiology, University of Magdeburg. Leipziger Strasse 44, D-39120 Magdeburg, Germany. gerburg.keilhoff@medizin.uni-magdeburg.de
Nitric oxide (NO) exerts both, pro-apoptotic and anti-apoptotic actions and appears to be acritical factor inneuronal degenerative and regenerative processes. NO is synthesized from L-arginine by NO synthase occurring in three isoforms of (neuronal, nNOS; endothelial, eNOS; inducible, iNOS). In a mice sciatic nerve model the regenerative outcome was assessed when the endogenous NO supply was deficient by knocking out the respective NOS isoform and compared to that of wild type mice after nerve transection. In nNOS knock-out mice a delay in regeneration, preceded by slowedWallerian degeneration and a disturbed pruning of uncontrolled sprouts, was observed. This was associated with a delayed recovery of sensory and motor function. Additionally, deficiency of nNOS led after nerve cut to a substantial loss of small and medium-sized dorsal root ganglia neurons, spinal cord interneurons and, to a lesser extent, spinal cord motor neurons. A lack of iNOS resulted in a delayed Wallerian degeneration and impaired regenerative outcome without consequences for neuronal survival. A lack of eNOS was well tolerated, although a delay in nerve revascularization was observed. Thus, after peripheral nerve lesion, regular NOS activity is essential for cell survival and recovery with reference to the nNOS isoform.
PMID: 14656046 [PubMed - in process]
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Expression and activity of arginase isoenzymes during normal and diabetes-impaired skin repair.
Kampfer H, Pfeilschifter J, Frank S.
Pharmazentrum Frankfurt, Klinikum der Johann Wolfgang Goethe-Universitat, Frankfurt am Main, Germany.
Within the past years, an important role for nitric oxide (NO) in skin repair has been well defined. As NO is synthesized from L-arginine by NO synthases (NOS), the availability of L-arginine might be one rate-limiting factor of NO production at the wound site. Upon injury, arginase-1 and -2 mRNA, protein, and activity were strongly induced reaching a maximum between day 3 and day 7 postwounding. Immunohistochemistry colocalized both arginases and the inducible NOS (iNOS) at epithelial sites at the margins of the wound. Notably, diabetes-impaired skin repair in leptin-deficient mice (diabetes/diabetes, db/db; and obese/obese, ob/ob) was characterized by an abnormally elevated arginase activity in wound tissue in the absence of an expression of iNOS. Expression analyses demonstrated that arginase-1 contributed to increased arginase activities in impaired repair. Interestingly, an improved healing of chronic wound situations in leptin-supplemented ob/ob mice was strongly associated with an adjustment of the dysregulated expression of L-arginine-converting enzymes: an attenuated iNOS expression was upregulated early in repair and an augmented arginase-1 expression and activity was downregulated in the presence of markedly elevated numbers of macrophages during late repair. These data suggest a coordinated consumption of L-arginine by the NOS and arginase enzymatic pathways at the wound site as a prerequisite for a balanced NO (via iNOS) and polyamine (via arginases) synthesis that drives a normal skin repair.
PMID: 14675208 [PubMed - in process]
[In Process Citation]7
Karowicz-Bilinska A, Kowalska-Koprek U, Suzin J, Sieroszewski P.
Kliniki Patologii Ciazy Instytutu Ginekologii i Poloznictwa UM w Lodzi.
Intrauterine growth restriction is connected with high rate of prematurity and perinatal mortality. 8-isoprostane is one of the oxidative stress indices, similar to the prostaglandins and connected with vessels restriction. The main aim of the study was to find the correlation between the L-arginine and acetylsalicylic acid therapy and 8-isoprostane concentration. MATERIAL AND METHODS: The study was done in Dep. of Obstetrics and Gynaecology Medical University in Lodz in 2000-2002 y. The study group consist of 50 women with diagnosed IUGR, the controls: 30 healthy pregnant women at the same gestational age. The IUGR therapy consisted of L-arginine 3 x 1 g and acetylsalicylic acid--Acard 1 x 1 daily. 8-isoprostane was measured in maternal blood in first and 20-th day of observation. The Oxis Immunoassay for 8-epi prostaglandin was used. The results were expressed in ng/ml of serum. RESULTS: The concentration of 8-isoprostaneat the first day of observation in women with IUGR was 0.0587 ng/ml, and after 20 days decreased to 0.0569. In women in normal pregnancy at the first day was 0.0539 ng/ml and after 20 days 0.0547 ng/ml. CONCLUSIONS: The 8-isoprostane concentration increased in blood serum due to the pregnancy duration. The therapeutic method decreased the concentration of this oxidative stress marker.
PMID: 14669408 [PubMed - in process]
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