Associations between Aging and Vitamin D Status with Whole-Body Nitric Oxide Production and Markers of Endothelial Function

Ageing and vitamin D deficiency have been associated with reduced nitric oxide (NO) synthesis and impaired endothelial function (EF) but the evidence in humans remains weak. Two independent cross-sectional studies were designed to evaluate the association between age, sex and plasma vitamin D concentrations with physiological and biochemical biomarkers of NO synthesis and EF in young and older healthy participants (Study-1) and in overweight and obese post-menopausal women (Study-2). In Study-1, forty young (20-49years) and older (50-75years) males and females (10 participants per age and sex group) were included. Resting blood pressure and ear-to-finger peripheral pulse wave velocity (PWV) were measured. A stable isotopic method was used to determine whole-body NO production. Plasma 25-hydroxyvitamin D (25(OH)D), nitrate, nitrite, and asymmetric dimethyl-arginine (ADMA) concentrations were determined. In Study-2, eighty older overweight and obese women (age 61.2±6.2years, BMI 29.5±4.4kg/m2) were recruited. Post-occlusion reactive hyperaemia (PROH) and peripheral PWV were measured. Plasma concentrations of 25(OH)D, nitrate, cyclic guanosine monophosphate (cGMP), 3-nitrotyrosine (3-NT), endothelin-1 (ET-1), vascular endothelial growth factor (VEGF), and ADMA were determined. In Study-1, whole-body NO production was significantly greater in young compared with older participants (0.61±0.30μmol·hr-1·kg-1 vs 0.39±0.10μmol·hr-1·kg-1, p=0.01) but there was no evidence of a sex difference (p=0.81). Plasma 25(OH)D concentration was not associated with PWV (r=0.18, p=0.28) or whole-body NO production (r=-0.20, p=0.22). Plasma ADMA concentration was associated positively with age (r=0.35, p=0.03) and negatively with whole-body NO production (r=-0.33, p=0.04). In Study-2, age was associated with lower PORH (r=-0.28, p=0.02) and greater ADMA concentrations (r=0.22, p=0.04). Plasma 25(OH)D concentration was inversely associated with 3-NT concentrations (r=-0.31, p=0.004). Older age was associated with lower whole-body NO production. Plasma vitamin D concentrations were not associated with NO production or markers of EF but showed a weak, significant correlation with oxidative stress in post-menopausal overweight women.