L-Arginine Therapy in Acute Myocardial Infarction

Schulman, Steven P.; Becker, Lewis C.; Kass, David A.; Champion, Hunter C.; Terrin, Michael L.; Forman, Sandra; Ernst, K; Kelemen, Mark D.; Townsend, Susan N.; Capriotti, Anne; Hare, Joshua M.; Gerstenblith, Gary

doi:10.1001/jama.295.1.58

Cited by 315 publications

(82 citation statements)

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“…Thus, understanding its metabolism in vascular health and disease is critical (23)(24)(25). Some studies have demonstrated a beneficial effect of arginine supplementation in patients with hypertension, angina, and erectile dysfunction (19), whereas a clinical trial with 6 months of arginine supplementation in patients with acute myocardial infarction (21) failed to demonstrate any vascular benefit. Increased arginine catabolism may provide an explanation for this.…”

Section: Discussionmentioning

confidence: 99%

“…In addition to serving as a substrate for NOS, arginine has vasodilatory, anti-inflammatory, and antiatherosclerotic properties (19,20). Although a recent study (21) failed to demonstrate a beneficial effect of arginine to decrease atherothrombotic events in the setting of acute myocardial infarction, this may have been explained by accelerated arginine catabolism secondary to increased arginase activity. Our objective was to measure arginase activity in plasma of subjects with uncomplicated type 2 diabetes and age-/BMI-matched nondiabetic control subjects and to examine the effect of physiologic hyperinsulinemia on plasma arginase activity.…”

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confidence: 98%

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Insulin Reduces Plasma Arginase Activity in Type 2 Diabetic Patients

et al. 2008

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OBJECTIVE -We sought to determine whether dysregulation of arginine metabolism is related to insulin resistance and underlies impaired nitric oxide (NO) generation in type 2 diabetic patients.RESEARCH DESIGN AND METHODS -We measured plasma arginase activity, arginine metabolites, and skeletal muscle NO synthase (NOS) activity in 12 type 2 diabetic and 10 age-/BMI-matched nondiabetic subjects before and following a 4-h euglycemichyperinsulinemic clamp with muscle biopsies. Arginine metabolites were determined by tandem mass spectroscopy. Arginase activity was determined by conversion of [14 C] guanidoinoarginine to [14 C] urea.RESULTS -Glucose disposal (R d ) was reduced by 50% in diabetic versus control subjects. NOS activity was fourfold reduced in the diabetic group (107 Ϯ 45 vs. 459 Ϯ 100 pmol ⅐ min Ϫ1⅐ mg protein Ϫ1 ; P Ͻ 0.05) and failed to increase with insulin. Plasma arginase activity was increased by 50% in the diabetic versus control group (0.48 Ϯ 0.11 vs. 0.32 Ϯ 0.12 mol ⅐ ml Ϫ1 ⅐ h Ϫ1 ; P Ͻ 0.05) and markedly declined in diabetic subjects with 4-h insulin infusion (to 0.13 Ϯ 0.04 mol ⅐ ml Ϫ1 ⅐ h Ϫ1 vs. basal; P Ͻ 0.05). In both groups collectively, plasma arginase activity correlated positively with fasting plasma glucose (R ϭ 0.46, P Ͻ 0.05) and A1C levels (R ϭ 0.51, P Ͻ 0.02) but not with R d .CONCLUSIONS -Plasma arginase activity is increased in type 2 diabetic subjects with impaired NOS activity, correlates with the degree of hyperglycemia, and is reduced by physiologic hyperinsulinemia. Elevated arginase activity may contribute to impaired NO generation in type 2 diabetes, and insulin may ameliorate this defect via reducing arginase activity. Diabetes Care 31:134-139, 2008T ype 2 diabetes is an insulin-resistant state characterized by inflammation, oxidative stress, and accelerated atherosclerosis (1-3). Nitric oxide (NO) bioavailability, critical for normal vasomotor tone and function, is reduced in states of insulin resistance, including type 2 diabetes (4,5). In addition to enhancing endothelial function, NO has been shown to modulate insulin sensitivity and glucose disposal (6,7). Activation of NO synthase (NOS) augments blood flow to insulin-sensitive tissues (i.e., skeletal muscle, liver, adipose tissue), and its activity has been shown to be impaired by hyperglycemia and insulin resistance (8,9). Under conditions of low arginine levels, NOS is uncoupled, producing reactive oxygen species and oxidative stress in lieu of NO (10). Increased oxidative stress and concentrations of asymmetric dimethylarginine (ADMA), in turn, further reduce NO bioavailability and are predictive of cardiovascular risk (11).Previous reports have related increased ADMA, oxidative stress, and endothelial dysfunction in type 2 diabetes and obesity to the severity of insulin resistance (11,12). Our lab (13) and others (14,15) have previously demonstrated reduced NOS activity in patients with type 2 diabetes and an impaired ability of insulin to increase NOS activity compared with healthy nondiabetic subjects. However...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 98%

Insulin Reduces Plasma Arginase Activity in Type 2 Diabetic Patients

et al. 2008

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“…Although these doses of L-arginine appear to be safe, no long term studies in humans have been published at this time and there are concerns of a pro-oxidative effect or even an increase in mortality in patients who may have severely dysfunctional endothelium, advanced atherosclerosis, CHD, ACS or MI [142] . In addition to the arginine-NO path, there exists an nitrate/nitrite pathway that is related to dietary nitrates from vegetables, beetroot juice and the DASH diet that are converted to nitrites by symbiotic, salivary, GI and oral bacteria [143] . Administration of beetroot juice or extract at 500 mg/d will increase nitrites and lower BP, improve endothelial function, increase cerebral, coronary and peripheral blood flow [143] .…”

Section: Proteinmentioning

confidence: 99%

“…In addition to the arginine-NO path, there exists an nitrate/nitrite pathway that is related to dietary nitrates from vegetables, beetroot juice and the DASH diet that are converted to nitrites by symbiotic, salivary, GI and oral bacteria [143] . Administration of beetroot juice or extract at 500 mg/d will increase nitrites and lower BP, improve endothelial function, increase cerebral, coronary and peripheral blood flow [143] . L-carnitine and acetyl -L-carnitine: L-carnitine is a nitrogenous constituent of muscle primarily involved in the oxidation of fatty acids in mammals.…”

Section: Proteinmentioning

confidence: 99%

The role of nutrition and nutraceutical supplements in the treatment of hypertension

Houston¹

2014

WJC

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Vascular biology, endothelial and vascular smooth muscle and cardiac dysfunction play a primary role in the initiation and perpetuation of hypertension, cardiovascular disease and target organ damage. Nutrientgene interactions and epigenetics are predominant factors in promoting beneficial or detrimental effects in cardiovascular health and hypertension. Macronutrients and micronutrients can prevent, control and treat hypertension through numerous mechanisms related to vascular biology. Oxidative stress, inflammation and autoimmune dysfunction initiate and propagate hypertension and cardiovascular disease. There is a role for the selected use of single and component nutraceutical supplements, vitamins, antioxidants and minerals in the treatment of hypertension based on scientifically controlled studies which complement optimal nutrition, coupled with other lifestyle modifications.© 2014 Baishideng Publishing Group Co., Limited. All rights reserved.Key words: Hypertension; Nutrition; Nutritional supplements; Cardiovascular disease; Vascular biology Core tip: Vascular biology and endothelial dysfunction play a primary roles in hypertension and subsequent cardiovascular disease. Micronutrients, macronutrients and optimal nutrition and nutritional supplements can prevent, control and treat hypertension through numerous mechanisms related to vascular biology. These treatments are complementary to drug therapy. Oxidative stress, inflammation and autoimmune dysfunction initiate and propagate hypertension and cardiovascular disease. There is a role for the selected use of single and component nutraceutical supplements, vitamins, antioxidants and minerals in the treatment of hypertension based on scientifically controlled studies which complement optimal nutrition, coupled with other lifestyle modifications.Houston M. The role of nutrition and nutraceutical supplements in the treatment of hypertension. World J Cardiol 2014; 6(2): 38-66 Available from:

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“…This trial was terminated early by the data and safety monitoring board when 8 deaths occurred in the arginine treated group [78].…”

Section: How Hard Is the Evidence?mentioning

confidence: 99%