Association of circulating uric acid and angiotensin-(1-7) in relation to higher blood pressure in adolescents and the influence of preterm birth

Elevated serum uric acid increases the risk of hypertension, and individuals born preterm have higher blood pressure (BP) and uric acid, but the mechanisms remain unclear. Preclinical studies demonstrate uric acid increases BP via increased renin-angiotensin system (RAS) expression, especially angiotensin (Ang) II, but the association of uric acid with Ang-(1–7) is unknown. Ang-(1–7), an alternative RAS product, counteracts Ang II by stimulating sodium excretion, vasodilation, and nitric oxide, thus contributing to lower BP. Plasma Ang-(1–7) is lower in preterm-born adolescents. We hypothesized uric acid is associated with a higher ratio of Ang II to Ang-(1–7) in plasma, especially in preterm-born adolescents. We measured BP, serum uric acid, and plasma RAS components in a cross-sectional analysis of 163 14-year-olds (120 preterm, 43 term). We estimated the associations between uric acid and the RAS using generalized linear models adjusted for sex, obesity, sodium intake, and fat intake, stratified by birth status. Uric acid was positively associated with Ang II/Ang-(1–7) (adjusted β (aβ): 0.88 mg/dl, 95% CI 0.17 to 1.58), plasma renin activity (aβ: 0.32 mg/dl, 95% CI 0.07 to 0.56), and aldosterone (aβ: 1.26 mg/dl, 95% CI 0.18 to 2.35), and inversely with Ang-(1–7) (aβ: −1.11 mg/dl, 95% CI −2.39 to 0.18); preterm birth did not modify these associations. Higher Ang II/Ang-(1–7) was associated with higher uric acid in adolescents. As preterm birth is associated with higher BP and uric acid, but lower Ang-(1–7), the imbalance between uric acid and Ang-(1–7) may be an important mechanism for the development of hypertension.