5 results on '"Böger R"'
Search Results
2. Asymmetric dimethylarginine (ADMA): a novel risk factor for endothelial dysfunction: its role in hypercholesterolemia.
- Author
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Böger RH, Bode-Böger SM, Szuba A, Tsao PS, Chan JR, Tangphao O, Blaschke TF, and Cooke JP
- Subjects
- Arginine blood, Arginine therapeutic use, Double-Blind Method, Female, Humans, Hypercholesterolemia drug therapy, Hypercholesterolemia enzymology, Injections, Intravenous, Male, Middle Aged, Nitric Oxide Synthase metabolism, Nitric Oxide Synthase Type III, Osmolar Concentration, Risk Factors, Arginine analogs & derivatives, Endothelium, Vascular physiopathology, Hypercholesterolemia blood, Hypercholesterolemia physiopathology
- Abstract
Background: Asymmetric dimethylarginine (ADMA) is an endogenous competitive inhibitor of nitric oxide (NO) synthase. Because endothelial NO elaboration is impaired in hypercholesterolemia, we investigated whether plasma concentrations of ADMA are elevated in young, clinically asymptomatic hypercholesterolemic adults. We further studied whether such elevation of ADMA levels was correlated with impaired endothelium-dependent, NO-mediated vasodilation and urinary nitrate excretion. In a randomized, double-blind, placebo-controlled study, we investigated whether these changes could be reversed with exogenous L-arginine., Methods and Results: We measured plasma levels of L-arginine, ADMA, and symmetrical dimethylarginine (SDMA) by high-performance liquid chromatography in 49 hypercholesterolemic (HC) and 31 normocholesterolemic (NC) humans. In 8 HC subjects, endothelium-dependent forearm vasodilation was assessed before and after an intravenous infusion of L-arginine or placebo and compared with 8 NC control subjects. ADMA levels were significantly elevated by >100% (2.17+/-0.15 versus 1.03+/-0.09 micromol/L; P<0.05) in HC subjects compared with NC adults. L-Arginine levels were similar, resulting in a significantly decreased L-arginine/ADMA ratio in HC subjects (27.7+/-2.4 versus 55. 7+/-5.4; P<0.05). In 8 HC subjects, intravenous infusion of L-arginine significantly increased the L-arginine/ADMA ratio and normalized endothelium-dependent vasodilation and urinary nitrate excretion. ADMA levels were inversely correlated with endothelium-mediated vasodilation (R=0.762, P<0.01) and urinary nitrate excretion rates (R=0.534, P<0.01)., Conclusions: We find that ADMA is elevated in young HC individuals. Elevation of ADMA is associated with impaired endothelium-dependent vasodilation and reduced urinary nitrate excretion. This abnormality is reversed by administration of L-arginine. ADMA may be a novel risk factor for endothelial dysfunction in humans.
- Published
- 1998
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3. Dietary L-arginine reduces the progression of atherosclerosis in cholesterol-fed rabbits: comparison with lovastatin.
- Author
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Böger RH, Bode-Böger SM, Brandes RP, Phivthong-ngam L, Böhme M, Nafe R, Mügge A, and Frölich JC
- Subjects
- Animals, Arginine administration & dosage, Arginine blood, Cholesterol blood, Cholesterol, Dietary administration & dosage, Cyclic GMP urine, Diet, Atherogenic, Endothelium, Vascular drug effects, Male, Nitrates urine, Nitric Oxide biosynthesis, Rabbits, Superoxides metabolism, Anticholesteremic Agents therapeutic use, Arginine therapeutic use, Arteriosclerosis drug therapy, Hypercholesterolemia drug therapy, Lovastatin therapeutic use
- Abstract
Background: We investigated whether L-arginine induces regression of preexisting atheromatous lesions and reversal of endothelial dysfunction in hypercholesterolemic rabbits, whether similar effects can be obtained by cholesterol-lowering therapy with lovastatin, and which mechanism leads to these effects., Methods and Results: Rabbits were fed 1% cholesterol for 4 weeks and 0.5% cholesterol for an additional 12 weeks. Two groups of cholesterol-fed rabbits were treated with L-arginine (2.0% in drinking water) or lovastatin (10 mg/d) during weeks 5 through 16. Systemic nitric oxide (NO) formation was assessed as the urinary excretion rates of nitrate and cGMP in weekly intervals. Cholesterol feeding progressively reduced urinary nitrate excretion to approximately 40% of baseline (P<.05) and increased plasma concentrations of asymmetrical dimethylarginine (ADMA), an endogenous NO synthesis inhibitor. Dietary L-arginine reversed the reduction in plasma L-arginine/ADMA ratio and partly restored urinary excretion of nitrate and cGMP (each P<.05 vs cholesterol) but did not change plasma cholesterol levels. L-Arginine completely blocked the progression of carotid intimal plaques, reduced aortic intimal thickening, and preserved endothelium-dependent vasodilator function. Lovastatin treatment reduced plasma cholesterol by 32% but did not improve urinary nitrate or cGMP excretion or endothelium-dependent vasodilation. Lovastatin had a weaker inhibitory effect on carotid plaque formation and aortic intimal thickening than L-arginine. L-Arginine inhibited but lovastatin potentiated superoxide radical generation in the atherosclerotic vascular wall., Conclusions: Dietary L-arginine improves NO-dependent vasodilator function in cholesterol-fed rabbits and completely blocks the progression of plaques via restoration of NO synthase substrate availability and reduction of vascular oxidative stress. Lovastatin treatment has a weaker inhibitory effect on the progression of atherosclerosis and no effect on vascular NO elaboration, which may be due to its stimulatory effect on vascular superoxide radical generation.
- Published
- 1997
- Full Text
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4. Biochemical evidence for impaired nitric oxide synthesis in patients with peripheral arterial occlusive disease.
- Author
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Böger RH, Bode-Böger SM, Thiele W, Junker W, Alexander K, and Frölich JC
- Subjects
- Adult, Aged, Aged, 80 and over, Aging metabolism, Arginine analogs & derivatives, Arginine blood, Arginine pharmacology, Cyclic GMP urine, Disease Progression, Enzyme Inhibitors pharmacology, Female, Humans, Male, Middle Aged, Nitrates urine, Nitric Oxide Synthase antagonists & inhibitors, Vasodilation physiology, Arterial Occlusive Diseases metabolism, Nitric Oxide biosynthesis, Nitric Oxide Synthase metabolism, Peripheral Vascular Diseases metabolism
- Abstract
Background: We studied urinary nitrate and cGMP excretion rates, indices of systemic NO formation, and plasma concentrations of L-arginine and the endogenous NO synthase inhibitor asymmetrical dimethylarginine (ADMA) and its inactive stereoisomer, symmetrical dimethylarginine, in 77 patients with peripheral arterial occlusive disease (PAOD) in Fontaine stages IIb through IV and in 47 young and 37 elderly healthy control subjects., Methods and Results: Urinary nitrate excretion was 182.0+/-11.4 micromol/mmol creatinine and cGMP excretion was 186.2+/-13.0 nmol/mmol creatinine in young healthy control subjects. In elderly control subjects, both excretion rates were slightly lower (nitrate, 156.0+/-7.8 micromol/mmol creatinine; cGMP, 150.0+/-8.3 nmol/mmol creatinine; P=NS). In PAOD patients, there was a significant, progressive reduction of urinary nitrate (IIb, 138.4+/-11.9; III, 128.6+/-11.3; and IV, 91.9+/-8.0 micromol/mmol creatinine; P<.05) and cGMP (IIb, 139.9+/-25.2; III, 115.6+/-13.1; and IV, 76.9+/-7.9 nmol/mmol creatinine; P<.05) excretion rates related to the Fontaine stage of PAOD. These changes were independent of changes in renal excretory function. Plasma L-arginine concentrations were not significantly different between the groups, but ADMA concentrations were elevated in PAOD patients (young control subjects, 1.25+/-0.11; elderly control subjects, 1.01+/-0.05 micromol/L; IIb, 2.62+/-0.24; III, 3.06+/-0.48; and IV, 3.49+/-0.26 micromol/L; P<.05 for PAOD versus control subjects). There was a significant linear correlation between urinary nitrate and cGMP excretion rates and a significant negative linear correlation between plasma ADMA concentrations and urinary nitrate excretion., Conclusions: In PAOD patients, there is a progressive reduction in urinary nitrate and cGMP excretion rates, which may be caused in part by accumulation of ADMA, an endogenous inhibitor of NO synthase.
- Published
- 1997
- Full Text
- View/download PDF
5. L-arginine induces nitric oxide-dependent vasodilation in patients with critical limb ischemia. A randomized, controlled study.
- Author
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Bode-Böger SM, Böger RH, Alfke H, Heinzel D, Tsikas D, Creutzig A, Alexander K, and Frölich JC
- Subjects
- Aged, Arterial Occlusive Diseases complications, Arterial Occlusive Diseases physiopathology, Humans, Injections, Intravenous, Ischemia etiology, Ischemia physiopathology, Male, Middle Aged, Arginine therapeutic use, Arterial Occlusive Diseases drug therapy, Extremities blood supply, Ischemia drug therapy, Nitric Oxide metabolism, Vasodilation drug effects
- Abstract
Background: L-Arginine is the precursor of endogenous nitric oxide (NO), which is a potent vasodilator acting via the intracellular second-messenger cGMP. In healthy humans, L-arginine induces peripheral vasodilation and inhibits platelet aggregation due to an increased NO production. Prostaglandin E1 (PGE1) induces peripheral vasodilation via stimulating prostacyclin receptors., Methods and Results: We investigated the effects of one intravenous infusion of L-arginine (30 g, 60 minutes) or PGE1 (40 microgram, 60 minutes) versus those of placebo (150 mL 0.9% saline, 60 minutes) on blood pressure, peripheral hemodynamics, and urinary NO3- and cGMP excretion rates in patients with critical limb ischemia (peripheral arterial occlusive disease stages Fontaine III or IV). Blood flow in the femoral artery was significantly increased by L-arginine (+42.3 +/- 7.9%, P<.05) and by PGE1 (+31.0 +/- 10.2%, P<.05) but not by placebo (+4.3 +/- 13.0%, P=NS). Urinary NO3- excretion increased by 131.8 +/- 39.5% after L-arginine (P<.05) but only by 32.3 +/- 17.2% after PGE1 (P=NS). Urinary cGMP excretion increased by 198.7 +/- 84.9% after L-arginine (P<.05) and by 94.2 +/- 58.8% after PGE1 (P=NS). Both urinary index metabolites were unchanged by placebo., Conclusions: We conclude that intravenous L-arginine induces NO-dependent peripheral vasodilation in patients with critical limb ischemia. These effects are paralleled by increased urinary NO3- and cGMP excretion, indicating an enhanced systemic NO production. Increased urinary NO3- excretion may be a sum effect of NO synthase substrate provision (L-arginine) and increased shear stress (PGE1 and L-arginine).
- Published
- 1996
- Full Text
- View/download PDF
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