Relationship between obesity, smoking, and the endogenous nitric oxide synthase inhibitor, asymmetric dimethylarginine

Eid, H.M.A.; Arnesen, Harald; Hjerkinn, Elsa M.; Lyberg, Torstein; Seljeflot, Ingebjørg

doi:10.1016/j.metabol.2004.06.026

Cited by 130 publications

(99 citation statements)

References 41 publications

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“…The elevated plasma levels of ADMA in subjects with a mean age of 70 years and without hypertension were even higher with hypertension [40]. A large study reported that plasma levels of ADMA were higher in elderly men than is usually reported in young, lean men, and were further increased in those who were obese [41]. We found no sex-related difference in SDMA or NMMA in any of our groups (Fig.…”

Section: Discussionsupporting

confidence: 47%

Elevations of plasma methylarginines in obesity and ageing are related to insulin sensitivity and rates of protein turnover

et al. 2005

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Elevations of plasma methylarginines in obesity and ageing are related to insulin sensitivity and rates of protein turnover Abstract Aims/hypothesis: Increased circulating methylarginines (MA) have been linked to the metabolic syndrome to explain endothelial dysfunction and cardiovascular disease risk. Proteins that contain MA are regulatory and release them during catabolism. We hypothesised that increased protein turnover in insulin-resistant states contributes to an increase in circulating MA. Materials and methods: We performed hyperinsulinaemic, euglycaemic, and isoaminoacidaemic experiments on 49 lean, obese and elderly subjects, with measurements of the kinetics of glucose and protein metabolism. Plasma MA, i.e. asymmetrical dimethylarginine (ADMA), symmetrical dimethylarginine (SDMA), and N G -monomethyl-L-arginine (NMMA), lipids and body composition were measured. Results: Insulin resistance of glucose and protein metabolism occurred in obese and elderly subjects. ADMA concentrations were 29 to 120% higher in obese and 34% higher in elderly than in lean subjects. SDMA were 34 and 20% higher in obese than in lean and than in elderly subjects, respectively. NMMA were 32% higher in obese than in lean subjects. ADMA differed by sex, being higher in men, namely by 1.75× in obese men and by 1.27× in elderly men. Postabsorptive ADMA (r=0.71), SDMA (r=0.46), and NMMA (r=0.31) correlated (all p<0.05) with rates of protein flux. All three MA correlated negatively with clamp glucose infusion rates and uptake (p<0.001). ADMA and SDMA correlated negatively with net protein synthesis and clamp amino acid infusion rates (p<0.05). All MA also correlated with adiposity indices and fasting insulin and triglycerides (p<0.05). Conclusions/ interpretation: Obesity, sex and ageing affect MA. Elevations of the three MA in obese, and of ADMA in elderly men, are related to increased protein turnover and to lesser insulin sensitivity of protein metabolism. These interrelationships might amplify insulin resistance and endothelial dysfunction.

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Section: Discussionsupporting

confidence: 47%

Elevations of plasma methylarginines in obesity and ageing are related to insulin sensitivity and rates of protein turnover

et al. 2005

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“…41 Recent clinical epidemiological studies in humans showed that the plasma NOx level was a little higher in smokers than in nonsmokers. 25,42 However, the difference was no longer significant after correction for some important clinical variables. 42 Moreover, Barua et al 40 and Rångemark and Wennmalm 43 reported no differences in the NOx level among smoking groups, which is similar to our findings.…”

Section: Discussionmentioning

confidence: 88%

C-reactive protein is associated with cigarette smoking-induced hyperfiltration and proteinuria in an apparently healthy population

et al. 2010

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Although cigarette smoking is known to be an important risk factor for renal disease, the mechanism by which smoking induces progressive renal disease in a healthy population has not been established. We hypothesized that oxidative stress (measured as 8-iso-prostaglandin F 2a , 8-iso-PGF2a), inflammation (highly sensitive C-reactive protein (CRP), hs-CRP) and nitric oxide may be associated with an alteration in the estimated glomerular filtration rate (eGFR) and proteinuria in otherwise healthy smokers. A total of 649 eligible subjects were classified according to their smoking status. Plasma NOx was measured using ozone-based chemiluminescence, urinary 8-iso-PGF2a was measured using enzyme immunoassay and serum hs-CRP was measured using a latex aggregation nephelometry method. The levels of 8-iso-PGF2a and hs-CRP increased in current smokers (P¼0.001 and P¼0.029, respectively), although there was not an increase in the NOx level. The prevalence of a high eGFR increased in light smokers (odds ratio (OR) 1.15 (95% confidence interval (CI), 0.61-2.17)) and heavy smokers (OR 2.33 (95% CI, 1.06-5.10)) when compared with non-and past smokers (P for trend¼0.024). The multivariable-adjusted mean values of the eGFR in current smokers, reported from the lowest to the highest quintiles of hs-CRP levels, were 82.1, 85.1, 86.4 and 88.5 ml per min per 1.73 m 2 (P for trend¼0.027). The mean values of proteinuria were 28.6, 34.6, 37.2 and 39.5 mg g À1 creatinine (P for trend¼0.003). The correlation coefficient between hs-CRP and eGFR was increased significantly (P¼0.03) across non-(r¼0.03), past (r¼À0.17), light (r¼0.13) and heavy smokers (r¼0.31). In conclusion, cigarette smoking is a risk factor for renal function alteration in healthy smokers and is characterized by a high eGFR and a high urinary protein associated with an increase in the hs-CRP. This finding suggests that hs-CRP may help mediate the alteration of renal function in smokers.

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“…The effect of smoking on plasma levels of ADMA has not been well characterized. In a large cross-sectional study, Eid et al 45 suggested that ADMA levels were lower in smokers; however, this study was performed in an elderly population, in which there was a high frequency of other risk factors for cardiovascular disease, making any direct interpretation on the effect of smoking, per se, on ADMA levels impossible.…”

Section: Discussionmentioning

confidence: 91%

Adverse Effects of Cigarette Smoke on NO Bioavailability

et al. 2006

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Abstract-Endothelial dysfunction is a hallmark of cardiovascular disease, and the L-arginine:NO pathway plays a critical role in determining endothelial function. Recent studies suggest that smoking, a well-recognized risk factor for vascular disease, may interfere with L-arginine and NO metabolism; however, this remains poorly characterized. Accordingly, we performed a series of complementary in vivo and in vitro studies to elucidate the mechanism by which cigarette smoke adversely affects endothelial function. In current smokers, plasma levels of asymmetrical dimethyl-arginine (ADMA) were 80% higher (Pϭ0.01) than nonsmokers, whereas citrulline (17%; PϽ0.05) and N-hydroxy-L-arginine (34%; PϽ0.05) were significantly lower. Exposure to 10% cigarette smoke extract (CSE) significantly affected endothelial arginine metabolism with reductions in the intracellular content of citrulline (81%), N-hydroxy-L-arginine (57%), and arginine (23%), while increasing ADMA (129%). CSE significantly inhibited (38%) arginine uptake in conjunction with a 34% reduction in expression of the arginine transporter, CAT1. In conjunction with these studies, CSE significantly reduced the activity of eNOS and NO production by endothelial cells, while stimulating the production of reactive oxygen species. In conclusion, cigarette smoke adversely affects the endothelial L-arginine NO synthase pathway, resulting in reducing NO production and elevated oxidative stress. In conjunction, exposure to cigarette smoke increases ADMA concentration, the latter being a risk factor for cardiovascular disease. Key Words: smoking Ⅲ endothelium Ⅲ metabolism A therosclerotic coronary and cerebrovascular disease are leading causes of death and disability in the Western world, and cigarette smoking has been clearly identified as a risk factor for coronary artery disease (reviewed by Ambrose and Barua 1 ). In this context, measures of endothelial function have been associated with cardiovascular outcome, 2 and smoking has been widely associated with reduced endothelial function. 3 The endothelium plays a central role in the modulation of vascular tone, the inhibition of platelet aggregation and vascular smooth muscle proliferation, and a key participation in angiogenesis under appropriate conditions. NO is well recognized as playing a pivotal part in these endothelial properties, being produced by the endothelial isoform of NO from its preferred substrate L-arginine. In this context, provision of sufficient L-arginine is critical for the sustained production of NO supply, 4 mediated in endothelial cells (ECs) principally by the type 1 cationic amino acid transporter (CAT1). Previous studies indicate that deleterious actions of cigarette smoke on endothelial function could be mitigated by supplemental L-arginine; 5 however, to date, the precise basis for this interaction remains unclear. One explanation is that cigarette smoke exerts an inhibitory effect on components of the L-arginine:NO pathway to influence NO production. In addition, potential effects of cigar...

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Relationship between obesity, smoking, and the endogenous nitric oxide synthase inhibitor, asymmetric dimethylarginine

Cited by 130 publications

References 41 publications

Elevations of plasma methylarginines in obesity and ageing are related to insulin sensitivity and rates of protein turnover

Elevations of plasma methylarginines in obesity and ageing are related to insulin sensitivity and rates of protein turnover

C-reactive protein is associated with cigarette smoking-induced hyperfiltration and proteinuria in an apparently healthy population

Adverse Effects of Cigarette Smoke on NO Bioavailability

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