Effects of L-arginine on impaired acetylcholine-induced and ischemic vasodilation of the forearm in patients with heart failure.

Hirooka, Yoshitaka; Imaizumi, Tsutomu; Shiramoto, Masanari; Endo, Toshihiko; Ando, Shin Ichi; Takeshita, Akira

doi:10.1161/01.cir.90.2.658

Cited by 136 publications

(72 citation statements)

References 42 publications

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“…Patients with hypertension, 8 -11 hypercholesterolemia, 15,16 congestive heart failure, 12,13 and diabetes mellitus 17,18 have impaired endothelial function. Our study suggests that OSA is associated with impaired resistance-vessel endothelial function, even in the absence of hypertension or other illnesses.…”

Section: Discussionmentioning

confidence: 99%

Impairment of Endothelium-Dependent Vasodilation of Resistance Vessels in Patients With Obstructive Sleep Apnea

et al. 2000

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Background —Patients with obstructive sleep apnea (OSA) experience repetitive episodic hypoxemia with consequent sympathetic activation and marked blood pressure surges, each of which may impair endothelial function. We tested the hypothesis that patients with OSA have impaired endothelium-dependent vasodilation, even in the absence of overt cardiovascular disease. Methods and Results —We studied 8 patients with OSA (age 44±4 years) and 9 obese control subjects (age 48±3 years). Patients with OSA were newly diagnosed, never treated for OSA, on no medications, and free of any other known diseases. All obese control subjects underwent complete overnight polysomnographic studies to exclude occult OSA. Resistance-vessel function was tested by use of forearm blood flow responses to intra-arterial infusions of acetylcholine (a vasodilator that stimulates endothelial release of nitric oxide), sodium nitroprusside (an exogenous nitric oxide donor), and verapamil (a calcium channel blocker). Conduit-vessel function was also evaluated by ultrasonography. Brachial artery diameter was measured under baseline conditions, during reactive hyperemia (with flow increase causing endothelium-dependent dilatation), and after sublingual administration of nitroglycerin (an endothelium-independent vasodilator). Patients with OSA had a blunted vasodilation in response to acetylcholine ( P <0.007), but responses to sodium nitroprusside and verapamil were not significantly different from those of control subjects. No significant difference in conduit-vessel dilation was evident between OSA patients and obese control subjects. Conclusions —Patients with OSA have an impairment of resistance-vessel endothelium-dependent vasodilation. This may be implicated in the pathogenesis of hypertension and heart failure in this condition.

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Section: Discussionmentioning

confidence: 99%

Impairment of Endothelium-Dependent Vasodilation of Resistance Vessels in Patients With Obstructive Sleep Apnea

et al. 2000

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“…In human heart failure, depressed vasodilator responses to acetylcholine have been observed in multiple vascular beds, including the forearm, 5,16,20,21 lower limb, 5 coronary circulation, 4,22 and isolated resistance arteries. 23 The finding of a beneficial effect of L-arginine supplementation 10,11,24 on endothelial function suggests that a relative deficiency of L-arginine, the key substrate for NO synthesis, may exist in heart failure. However, these observations do not distinguish whether the deficiency is extracellular or intracellular.…”

Section: Discussionmentioning

confidence: 99%

“…9 Recently, several groups have demonstrated an improvement in endothelial function in patients with heart failure in response to supplemental oral or intravenous L-arginine. 10,11 This strategy has also been shown to improve endothelial function in other clinical paradigms that are characterized by endothelial dysfunction, most notably atherosclerosis. [12][13][14] The observations that L-arginine supplementation can improve endothelial function may provide some insight into the mechanisms responsible for this phenomenon.…”

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confidence: 99%

In Vivo and In Vitro Evidence for Impaired Arginine Transport in Human Heart Failure

et al. 2000

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Background-The clinical features of congestive heart failure (CHF) result from a complex interaction between reduced ventricular function, neurohormonal activation, and impaired endothelial function. Although endothelial dysfunction has been well documented, the mechanisms that contribute to this abnormality remain unknown. Recent studies, however, indicate a potential therapeutic role for supplemental L-arginine, suggesting the presence of an underlying disorder of L-arginine metabolism. Methods and Results-We used 2 complementary approaches to assess L-arginine transport in control subjects and patients with CHF. During a steady-state intra-arterial infusion of [ 3 H]L-arginine (100 nCi/min), forearm clearance of [ 3 H]L-arginine was significantly reduced in CHF patients compared with forearm kinetics in control subjects (64Ϯ2 versus 133Ϯ14 mL/min, Pϭ0.002). In conjunction with this, [ 3 H]L-arginine uptake by peripheral blood mononuclear cells (PBMCs) was also substantially reduced in heart failure patients compared with controls (V max 10.1Ϯ1.3 versus 49.8Ϯ7.1 pmol/10 5 cells per 5 minutes, PϽ0.001). In association with this finding, we observed a 76% (PϽ0.01) reduction in mRNA expression for the cationic amino acid transporter CAT-1, as assessed by ribonuclease protection assay. Conclusions-These data document both in vivo and in vitro evidence for a marked depression of L-arginine transport in human CHF and therefore provide an explanation for the restorative actions of supplemental L-arginine on vascular function in

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“…ACh (Acetilcolina; USP, São Paulo, SP, Brazil) and SNP (NPS; Lebon, Porto Alegre, RS, Brazil), dissolved in 0.9% NaCl, were infused at rates of 0.2, 0.4, and 0.8 ml/min to assess different drug concentrations. For practical purposes, we decided to change the infusion rates of ACh and SNP to achieve different drug concentrations because it is well described that until the intra-arterial infusion reaches 1 ml/min, there is no detectable change in the blood flow measurement (16). ACh and SNP were infused at progressive doses of 7.5, 15, and 30 and 2, 4, and 8 g/min, respectively, for 5 min each.…”

Section: Endothelial Function Assessmentmentioning

confidence: 99%

Metformin Improves Endothelial Vascular Reactivity in First-Degree Relatives of Type 2 Diabetic Patients With Metabolic Syndrome and Normal Glucose Tolerance

et al. 2006

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OBJECTIVE -Endothelial dysfunction is an early marker of atherosclerosis seen in type 2 diabetic subjects. Metformin is commonly used in the treatment of type 2 diabetes and has known vasculoprotective effects beyond its hypoglycemic ones. We aimed to investigate the vascular effects of metformin in first-degree relatives with metabolic syndrome of type 2 diabetic patients.RESEARCH DESIGN AND METHODS -The study included 31 subjects (age 38.3 Ϯ 7.6 years and BMI 36.3 Ϯ 5.2 kg/m 2 ), who were first-degree relatives of type 2 diabetic patients and who had metabolic syndrome and normal glucose tolerance. The subjects were randomly assigned 1:1 in a double-blind fashion to receive placebo (n ϭ 15) or metformin (n ϭ 16). Endothelial function was assessed by venous occlusion plethysmography, measuring forearm blood flow (FBF) and vascular resistance responses to three intra-arterial infusions of endothelium-dependent (acetylcholine 7.5, 15, and 30 g/min) and independent (sodium nitroprusside 2, 4, and 8 g/min) vasodilators. Weight, BMI, systolic and diastolic blood pressure, waist, and laboratory parameters (lipid profile and fasting plasma glucose [FPG]) were assessed at baseline and after treatment.RESULTS -The metformin and placebo groups did not differ in anthropometric, clinical, laboratory, and vascular measurements at baseline. The metformin group had decreased weight, BMI, systolic blood pressure, and FPG and improved lipid profile. Endothelium-dependent FBF responses were also improved, without any effect on endothelium-independent responses. There was no correlation between the improvement on FBF responses and the observed changes on anthropometric, clinical, and laboratory parameters.CONCLUSIONS -We concluded that metformin improved vascular endothelial reactivity in first-degree relatives with metabolic syndrome of type 2 diabetic patients, independently of its known antihyperglycemic effects. Diabetes Care 29:1083-1089, 2006T he precocious and accelerated atherosclerosis seen in type 2 diabetes raised the question about pathogenetic factors that initiate the development of vascular derangements in the prediabetic population. Metabolic syndrome, a pre-diabetic state, comprises an array of cardiovascular risk factors such as abdominal obesity, dyslipidemia, hypertension, impaired glucose tolerance, and insulin resistance. Insulin resistance, the central abnormality for the pathogenesis of metabolic syndrome, is considered an independent risk factor for cardiovascular mortality in general (1) and in the diabetic population (2) in particular.The endothelium is an important locus for the control of vascular function. It actively regulates vascular tone, permeability to leukocytes and macromolecules, the balance between coagulation and fibrinolysis, composition of the subendothelial matrix, and proliferation of vascular smooth muscle cells. The great variety of beneficial functions attributed to the endothelium is mainly associated with nitric oxide (NO) bioavailability. In experimental studies of atherogenesis,...

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Effects of L-arginine on impaired acetylcholine-induced and ischemic vasodilation of the forearm in patients with heart failure.

Abstract: Our results suggest that defective endothelial function may contribute to impaired ischemic vasodilator capacity in HF.

Cited by 136 publications

References 42 publications

Impairment of Endothelium-Dependent Vasodilation of Resistance Vessels in Patients With Obstructive Sleep Apnea

Impairment of Endothelium-Dependent Vasodilation of Resistance Vessels in Patients With Obstructive Sleep Apnea

In Vivo and In Vitro Evidence for Impaired Arginine Transport in Human Heart Failure

Metformin Improves Endothelial Vascular Reactivity in First-Degree Relatives of Type 2 Diabetic Patients With Metabolic Syndrome and Normal Glucose Tolerance

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