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Effects of vitamin C on intracoronary L-arginine dependent coronary vasodilatation in patients with stable angina.
Tousoulis, D, Xenakis, C, Tentolouris, C, Davies, G, Antoniades, C, Crake, T, Stefanadis, C
Heart (British Cardiac Society). 2005;(10):1319-23
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Abstract
OBJECTIVE To assess the effects of intravenous vitamin C administration on the vasomotor responses to intracoronary L-arginine infusion in epicardial coronary arteries. METHODS 28 patients with coronary artery disease and stable angina were enrolled in the study. Eight patients received intracoronary infusions of 150 micromol/min L-arginine before and after intravenous infusion of vitamin C, 10 patients received intracoronary infusions of 150 micromol/min L-arginine before and after intravenous infusion of normal saline, and 10 patients received intracoronary normal saline before and after intravenous infusion of vitamin C. The diameter of proximal and distal coronary artery segments was measured by quantitative angiography. RESULTS Infusion of L-arginine caused significant dilatation of both proximal (4.87 (0.96)%, p < 0.01 v normal saline) and distal (6.33 (1.38)%, p < 0.01 v normal saline) coronary segments. Co-infusion of vitamin C and L-arginine dilated proximal coronary segments by 8.68 (1.40)% (p < 0.01 v normal saline, p < 0.01 v L-arginine) and distal segments by 13.07 (2.15)% (p < 0.01 v normal saline, p < 0.01 v L-arginine). Intravenous infusion of vitamin C caused a borderline increase in proximal and distal coronary segment diameters (1.93 (0.76)% and 2.09 (1.28)%, respectively, not significant). CONCLUSIONS L-arginine dependent coronary segment vasodilatation was augmented by the antioxidant vitamin C in patients with coronary artery disease. Thus, vitamin C may have beneficial effects on nitric oxide bioavailability induced by L-arginine.
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beta-Adrenoceptor-mediated, nitric-oxide-dependent vasodilatation is abnormal in early hypertension: restoration by L-arginine.
Schlaich, MP, Ahlers, BA, Parnell, MM, Kaye, DM
Journal of hypertension. 2004;(10):1917-25
Abstract
BACKGROUND It is unknown whether beta-adrenoceptor-mediated vasodilatation is altered in early hypertension and whether it can be modulated by L-arginine. METHODS AND DESIGN We measured changes in forearm blood flow by plethysmography in response to acetylcholine (9 and 37 microg/min), sodium nitroprusside (200 and 800 ng/min) and the beta-receptor agonist, isoproterenol (50 and 200 ng/min) in 12 patients with essential hypertension (group EH) and in healthy volunteers with (group PFH; n = 14) and without (group NFH; n = 14) a family history of essential hypertension, before and during concomitant infusion of L-arginine (10 micromol/min). In five individuals from each group, infusion of acetylcholine and isoproterenol was repeated during the concurrent blockade of nitric oxide synthesis by N-monomethyl-L-arginine (L-NMMA; 4 micromol/min). RESULTS The response to acetylcholine was reduced in groups EH and PFH compared with group NFH (both P < 0.05), whereas the vasodilator effects of isoproterenol and sodium nitroprusside were similar in all three groups. Acetylcholine- and isoproterenol-induced vasodilatation did not change during infusion of the nitric oxide precursor, L-arginine, in group NFH, but were significantly enhanced by L-arginine in groups PFH and EH [forearm blood flow before and after isoproterenol 200 ng/min: group PFH 11.8 +/- 1.02 and 13.3 +/- 1.08 ml/min, respectively (P < 0.05); group EH: 11.3 +/- 1.57 and 14.9 +/- 1.91 ml/min, respectively (P < 0.01)]. Co-infusion of L-NMMA blunted the response to acetylcholine and isoproterenol in group NFH (P < 0.05), but did not significantly modify vasodilatation in groups PFH and EH. CONCLUSIONS Although beta-adrenergic vasodilatation seemed to be unaltered in early hypertension, L-arginine enhanced the response to isoproterenol, whereas concomitant inhibition of nitric oxide synthase by L-NMMA had no significant effect. These findings suggest that the nitric oxide component of isoproterenol-mediated vasodilatation is impaired in early hypertension and possibly compensated by increased beta-adrenoceptor responsiveness of smooth muscle cells. In this setting, supplementation of the nitric oxide precursor, L-arginine, enhances the vasodilator response to beta-adrenergic stimulation.
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Decreased arginine bioavailability and increased serum arginase activity in asthma.
Morris, CR, Poljakovic, M, Lavrisha, L, Machado, L, Kuypers, FA, Morris, SM
American journal of respiratory and critical care medicine. 2004;(2):148-53
Abstract
Recent studies suggest that a nitric oxide (NO) deficiency and elevated arginase activity may play a role in the pathogenesis of asthma. Although much attention has been directed toward measurements of exhaled NO in asthma, no studies to date have evaluated levels of plasma arginase or arginine, the substrate for NO production, in patients with asthma. This study, therefore, measured amino acid levels, arginase activity, and nitric oxide metabolites in the blood of patients with asthma, as well as NO in exhaled breath. Although levels of virtually all amino acids were reduced, patients with asthma exhibited a striking reduction in plasma arginine levels compared with normal control subjects without asthma (45 +/- 22 vs. 94 +/- 29 microM, p < 0.0001), and serum arginase activity was elevated (1.6 +/- 0.8 vs. 0.5 +/- 0.3 micromol/ml/hour, asthma vs. control, p < 0.0001). High arginase activity in patients with asthma may contribute to low circulating arginine levels, thereby limiting arginine bioavailability and creating a NO deficiency that induces hyperreactive airways. Addressing the alterations in arginine metabolism may result in new strategies for treatment of asthma.
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Safe and effective inhibition of renal uptake of radiolabelled octreotide by a combination of lysine and arginine.
Rolleman, EJ, Valkema, R, de Jong, M, Kooij, PP, Krenning, EP
European journal of nuclear medicine and molecular imaging. 2003;(1):9-15
Abstract
As scintigraphy with [(111)In-DTPA(0)]octreotide has become a standard technique in analysing somatostatin receptor-receptor positive lesions such as neuroendocrine tumours, a logical next step is peptide receptor radionuclide therapy (PRRT). Initial studies on PRRT were performed with high doses of [(111)In-DTPA(0)]octreotide, and recently other radionuclides coupled to other somatostatin analogues have been used for this purpose. However, the dose delivered to the kidney is a major dose-limiting factor. Amino acid solutions have previously been used to reduce renal uptake of radioactivity, but these solutions have some disadvantages, i.e. their hyperosmolarity and their propensity to cause vomiting and metabolic changes. In this study we tested various amino acid solutions in patients receiving [(111)In-DTPA(0)]octreotide PRRT in order to assess their safety and their capacity to inhibit the renal uptake of radioactivity. Patients served as their own non-infused control. Renal radioactivity at 24 h following the injection of [(111)In-DTPA(0)]octreotide was inhibited by (1) a commercially available amino acid solution (AA) (21%+/-14%, P<0.02), (2) by 25 g (17%+/-9%, P<0.04), 50 g (15%+/-13%, P<0.04) or 75 g of lysine (44%+/-11%, P<0.001) and (3) by a combination of 25 g of lysine plus 25 g of arginine (LysArg) (33%+/-23%, P<0.01). Fluid infusion alone (500, 1,000 or 2,000 ml of saline/glucose) did not change renal uptake of radioactivity. In patients studied with 75 g of lysine (Lys75) and LysArg, serum potassium levels rose significantly. Maximal potassium levels were within the toxic range (6.3, 6.7 and 6.8 mmol/l) in three out of six patients infused with Lys75, whereas with LysArg the highest concentration measured was 6.0 mmol/l. Electrocardiographic analysis did not reveal significant changes in any of the patients. Vomiting occurred in 50% of patients infused with AA, but in only 6% of patients receiving no amino acid infusion (controls) and 9% of patients receiving LysArg. We conclude that co-infusion of Lys75 or LysArg results in a significant inhibition of renal radioactivity in PRRT, allowing higher treatment doses and thus resulting in higher tumour radiation doses. Because Lys75 produced serious hyperkalaemia, it is not suitable for clinical use. LysArg, however, is effective in offering renal protection in PRRT and is safe.
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Paradoxical decrease in plasma NOx by L-arginine load in diabetic and non-diabetic subjects.
Maejima, K, Himeno, M, Ishibashi, T, Nakano, S, Nishio, M, Uchida, K
Clinical and experimental hypertension (New York, N.Y. : 1993). 2002;(3):155-67
Abstract
L-arginine, a substrate of nitric oxide synthase, was infused (30 g/300 ml/30 min) to patients with or without type 2 diabetes to examine whether or not endothelial dysfunction expressed as attenuated depressor response to the substrate in diabetic patients may accompany attenuated plasma NOx (NO2- and NO3-; an index of NO formation) elevation. Decrease in blood pressure by L-arginine was significantly smaller in diabetic patients than that in non-diabetic patients, and increase in plasma cGMP level in diabetic patients tended to be smaller and retarded than non-diabetic patients. However, plasma NOx decreased in both groups in a similar degree without changes in urinary NOx excretion, implying that NOx in plasma moved to other compartments. These results indicate that plasma NOx could not be solely used as an index of NO formation by L-arginine load and that this paradoxical decrease in plasma NOx would require further examination extending to other NOx compartments.
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Effect of parenteral nutrition with L-arginine supplementation on postoperative immune function in patients with colorectal cancer.
Song, JX, Qing, SH, Huang, XC, Qi, DL
Di 1 jun yi da xue xue bao = Academic journal of the first medical college of PLA. 2002;(6):545-7
Abstract
OBJECTIVE To study the effects of parenteral nutrition (PN) supplemented with L-arginine on the immune function of patients with colorectal cancer after operation. METHODS Forty randomly chosen patients with colorectal cancer were enrolled in this study, who received either standard PN or PN supplemented with 20 g/d L-arginine for 7 d after surgical removal of the tumors. Tests of the immune function (CD3(+), CD4(+), CD8(+), CD4(+)/CD8(+), interleukin-2R, natural killer cells, C3, C4, CH50, IgA, IgM, IgG) were performed preoperatively and at different time periods postoperatively. RESULTS Data analysis with ANOVA demonstrated immune suppression in the patients before operation, and the condition was improved (as evidenced by increased CD4(+),CD4(+)/CD8(+), natural killer cells and interleukin-2R levels) in L-arginine group as compared with the results in the control group at days 4 and 7 (P<0.05). CONCLUSION Arginine can improve the immune function in patients with colorectal cancer after operation and enhance PN effect.
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Impairment of renal vasodilation with l-arginine is related to more severe disease in untreated hypertensive patients.
Bello, E, Caramelo, C, Martell, N, Alcázar, JM, González, J, López, MD, Ruilope, LM, González, FR, Rovira, AM, Gazapo, R, et al
Hypertension (Dallas, Tex. : 1979). 2001;(4):907-12
Abstract
Data remain insufficient to place the decreased response to L-arginine in hypertensive patients within a consistent pathophysiological sequence. The aim of the present study in patients with essential hypertension was to assess the relationships between the response to L-arginine and a set of relevant clinical and laboratory parameters. In this prospective, interventional study, we administered L-arginine to untreated hypertensive individuals and healthy control subjects and measured the clearance of inulin and of para-aminohippurate and a set of biochemical and clinical variables. L-Arginine infusion revealed major differences between control subjects and 1 subgroup (group B) of hypertensive individuals. Group B hypertensives (n=18) had no increase in inulin clearance and no decrease in renal vascular resistance with L-arginine; however, in another subset of hypertensive patients (group A, n=27), the insulin clearance increased and renal vascular resistance decreased similar to the control group (group C, n=11). The ambulatory blood pressure monitoring in group B showed both an increased mean diastolic pressure and a "nondipper" pattern in the nocturnal regulation of arterial pressure. These findings in group B were accompanied by significant alterations in optic fundus and left ventricle hypertrophy and increased microalbuminuria (all, P<0.05). Furthermore, group B individuals had significantly lower values of HDL cholesterol and a higher baseline atherogenic index, plasma insulin level, and glucose/insulin index. We disclose a previously undescribed relationship between end organ repercussion and decreased renal hemodynamic response to L-arginine. Our results may help to understand the mechanisms that lead to target organ damage in hypertension.