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

Abstract

Background: Aging 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.

Objectives: 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 postmenopausal females (Study 2).

Methods: In Study 1, 40 young (20-49 y) and older (50-75 y) 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 dimethylarginine (ADMA) concentrations were determined. In Study 2, 80 older overweight and obese females (age 61.2 ± 6.2 y, body mass index 29.5 ± 4.4 kg/m²) were recruited. Postocclusion reactive hyperemia (PORH) and peripheral PWV were measured. Plasma concentrations of 25(OH)D, nitrate, cyclic guanosine monophosphate, 3-nitrotyrosine (3-NT), endothelin-1, vascular endothelial growth factor, and ADMA were determined.

Results: In Study 1, whole-body NO production was significantly greater in young compared with older participants (0.61 ± 0.30 μmol·h^-1·kg^-1 compared with 0.39 ± 0.10 μmol·h^-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).

Conclusions: 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 postmenopausal overweight females.

Keywords: aging; endothelial function; nitric oxide; pulse wave velocity; vitamin D.