Effects of acute and chronic stress on the L-arginine nitric oxide pathway in black and white South Africans: the sympathetic activity and ambulatory blood pressure in Africans study.

OBJECTIVE: This study investigated the impact of stress on effectors of the L-arginine/nitric oxide (NO) system including the endogenous inhibitor asymmetric dimethylarginine (ADMA). METHODS: Black (n = 168) and white (n = 206) South African teachers were exposed to a mental and a physical stressor for 1 minute, respectively. Serum samples for determination of l-arginine, NO metabolites, ADMA, and symmetric dimethylarginine (SDMA) were obtained at rest and during stress exposure. Perception of task stressfulness was assessed on a 7-point Likert scale, and psychological distress was estimated by the General Health Questionnaire. RESULTS: Black South Africans exhibited higher resting levels of NO metabolites (adjusted mean [standard error of the mean] = 11.3 [1.3] versus 3.9 [1.1] µmol/l, p < .001) but lower circulating ADMA (0.62 [0.02] versus 0.70 [0.02] µmol/l, p = .004) and SDMA (0.41 [0.01] versus 0.53 [0.01] µmol/l, p < .001) than did white South Africans. Ethnicity-by-psychological distress interaction was observed for resting levels of ADMA (p = .002), SDMA (p = .038), and L-arginine (p = .048). Ethnic differences in responses to experimental stress were evident for NO metabolites (blacks versus whites: 5.94 [1.55] versus -0.74 [1.25] µmol/l, p = .004) and SDMA (blacks versus whites: -0.02 [0.01] versus 0.02 [0.01] µmol/l, p = .004). Ethnicity-by-psychological distress interaction for stress responses was found for l-arginine/ADMA ratio (p = .027). CONCLUSIONS: The l-arginine/NO system is affected by psychosocial distress with higher susceptibility in black South Africans. This interaction may contribute to the higher cardiovascular disease risk in black South Africans.

Central systolic blood pressure relates inversely to nitric oxide synthesis in young black adults: the African-PREDICT study.

Lower nitric oxide (NO) bioavailabilty associates with hypertension in patients and elderly populations. With hypertension known to develop earlier in black populations, we compared both plasma and urinary NO-related markers and their associations with central systolic blood pressure (cSBP) and arterial stiffness in healthy young black and white adults. We included healthy black and white men and women (n = 1110; 20-30 years) and measured cSBP and pulse wave velocity (PWV), along with both plasma and urinary arginine, homoarginine, asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), as well as urinary ornithine/citrulline, nitrite and nitrate. In addition, the urinary nitrate-to-nitrite ratio (UNOxR) was calculated. The black men and women had higher cSBP and higher plasma arginine and ADMA, but lower urinary nitrate and UNOxR (all p ≤ 0.003) than their white counterparts. In single and forward stepwise multiple regression analyses, we found an inverse association of cSBP (adj. R2 = 0.124; ß = -0.134; p = 0.006) and plasma homoarginine in black men. Central SBP associated inversely with UNOxR in black women only (adj. R2 = 0.171; ß = -0.130; p = 0.029). In the white women, cSBP associated positively with urinary ADMA (adj. R2 = 0.372; ß = 0.162; p = 0.015). PWV associated inversely with plasma ADMA (adj. R2 = 0.253; ß = -0.163; p = 0.024) in the white women only. The lower NO synthesis and the higher cSBP in our black cohort support the notion of a potential increased risk for future large artery stiffness and hypertension development in later life.

An additive effect of endothelial nitric oxide synthase gene polymorphisms contributes to the severity of atherosclerosis in patients on dialysis.

BACKGROUND: Reduced synthesis of nitric oxide (NO) is considered a major proatherogenic mechanism in patients with end-stage renal disease (ESRD), but genetic factors impinging on this mechanism have been little studied in this population. METHODS: We tested the relationship between carotid intima-media thickness (IMT) and three endothelial NO synthase (eNOS) polymorphisms (G894T, T-786C, and 27-bp repeat in intron 4) in an ethnically and geographically homogeneous group of 147 patients with ESRD. RESULTS: The IMT was significantly thicker (P = .01) in patients with the TT genotype (G894T polymorphism) than in patients with TG or GG genotypes, and a similar association was observed for the T-786C polymorphism (P = .02). These relationships remained statistically significant (P = .02 and .01), also in multivariate models including traditional and emerging risk factors for atherosclerosis. Moreover, there was a direct association between the number of risk alleles and IMT (no risk allele: 0.97 +/- 0.22 mm, 1 risk allele: 1.03 +/- 0.20 mm, 2 risk alleles: 1.07 +/- 0.22 mm, > or =3 risk alleles: 1.23 +/- 0.36 mm, P < .001) that remained statistically significant in a multiple regression model. CONCLUSIONS: In patients on dialysis the risk alleles of G894T and T-786C polymorphisms of the eNOS gene are associated with carotid atherosclerosis. The additive effect of the two polymorphisms may contribute to the severity of atherosclerosis independently of other risk factors and of endogenous substances that influence the NO synthesis in this population.

Atherosclerosis and the Glu298Asp polymorphism of the eNOS gene in white patients with end-stage renal disease.

BACKGROUND: We investigated whether the eNOS G/T polymorphism (Glu298Asp variant) is linked to the severity of carotid atherosclerosis and whether it is independent of asymmetric dimethylarginine (ADMA) in determining vascular damage in patients with end-stage renal disease (ESRD). METHODS: The eNOS polymorphism, ADMA, carotid intima-media thickness (IMT), and carotid artery (CCA) wall-to-lumen ratio (an indicator of arterial remodeling) were determined/measured in 131 patients with ESRD. RESULTS: Both in the co-dominant and dominant model approach, IMT as well as CCA wall-to-lumen ratio were directly related to the T allele (P < or = .009) and these relationships held true in multiple linear regression analyses including ADMA and traditional and emerging risk factors. The relationship between eNOS genotypes and CCA wall-to-lumen ratio was further analyzed by a categorical approach and in a multiple logistic regression analysis, the odds ratio (OR) of increased CCA wall-to-lumen ratio was strongly associated to the T allele (codominant model: GG, OR = 1; GT, OR = 2.1; TT, OR = 8.2; P for trend = .01; dominant model: GG, OR = 1; GT and TT, OR = 2.7; P = .02). CONCLUSIONS: The T allele of eNOS gene is an independent predictor of intimal lesions and vascular remodeling and it is associated with the severity of atherosclerosis independently of ADMA.

Effects of moderate hyperhomocysteinaemia induced by 4 weeks methionine-enriched diet on metabolite profile and mesenteric artery function in rats.

Methionine is an essential amino acid and methyl donor for most transmethylation reactions in mammals. The product of transmethylation reactions is homocysteine, which is associated with enhanced risk for CVD. The aim of this study was to analyse metabolic and vascular functional consequences of a methionine-enriched diet in rats. The dose of methionine was chosen to reflect the range of over-nutrition in man. We quantified plasma levels of homocysteine, asymmetrical dimethylarginine and adenosine, determined methionine and its metabolites in tissues and blood plasma and assessed relaxation of mesenteric arteries toward acetylcholine and sodium nitroprusside. A methionine-enriched diet for 4 weeks elevated homocysteine levels in plasma 2-fold and in spleen by 70 %. The level of S-adenosylhomocysteine was increased in liver only, while methionine and S-adenosylmethionine were unchanged in all organs studied. Plasma adenosine and asymmetrical dimethylarginine levels were unchanged, as were vessel relaxations. A 2-fold elevation of plasma homocysteine, which is assigned a risk indicator for cardiovascular events, did not impair mesenteric artery vasodilatation during 4 weeks of a methionine-rich diet. Furthermore, asymmetrical dimethylarginine and adenosine, which have been shown to be changed in more severe degrees of hyperhomocysteinaemia, remained unaltered.