Association between blood pressure and angiotensin-converting enzymes activity in prepubertal children ∗.

OBJECTIVES: Angiotensin-converting enzymes' (ACEs) relationship with blood pressure (BP) during childhood has not been clearly established. We aimed to compare ACE and ACE2 activities between BMI groups in a sample of prepubertal children, and to characterize the association between these enzymes' activities and BP. METHODS: Cross-sectional study of 313 children aged 8-9 years old, included in the birth cohort Generation XXI (Portugal). Anthropometric measurements and 24-h ambulatory BP monitoring were performed. ACE and ACE2 activities were quantified by fluorometric methods. RESULTS: Overweight/obese children demonstrated significantly higher ACE and ACE2 activities, when compared to their normal weight counterparts [median (P25-P75), ACE: 39.48 (30.52-48.97) vs. 42.90 (35.62-47.18) vs. 43.38 (33.49-49.89) mU/ml, P for trend = 0.009; ACE2: 10.41 (7.58-15.47) vs. 21.56 (13.34-29.09) vs. 29.00 (22.91-34.32) pM/min per ml, P for trend < 0.001, in normal weight, overweight and obese children, respectively]. In girls, night-time systolic BP (SBP) and diastolic BP (DBP) increased across tertiles of ACE activity ( P < 0.001 and P  = 0.002, respectively). ACE2 activity was associated with higher night-time SBP and DBP in overweight/obese girls ( P  = 0.037 and P  = 0.048, respectively) and night-time DBP in the BMI z-score girl adjusted model ( P  = 0.018). Median ACE2 levels were significantly higher among nondipper girls (16.7 vs. 11.6 pM/min per ml, P  = 0.009). CONCLUSIONS: Our work shows that obesity is associated with activation of the renin-angiotensin-aldosterone system, with significant increase of ACE and ACE2 activities already in childhood. Also, we report sex differences in the association of ACE and ACE2 activities with BP.

Oxidative stress and nitric oxide are increased in obese children and correlate with cardiometabolic risk and renal function.

Oxidative stress and nitric oxide (NO) appear to represent important links between obesity and cardiovascular, metabolic and/or renal disease. We investigated whether oxidative stress and NO production/metabolism are increased in overweight and obese prepubertal children and correlate with cardiometabolic risk and renal function. We performed a cross-sectional evaluation of 313 children aged 8-9 years. Anthropometrics, 24-h ambulatory blood pressure, pulse wave velocity (PWV), insulin resistance (homoeostasis model assessment index (HOMA-IR)), inflammatory/metabolic biomarkers, estimated glomerular filtration rate (eGFR), plasma total antioxidant status (TAS), plasma and urinary isoprostanes (P-Isop, U-Isop), urinary hydrogen peroxide (U-H2O2), and plasma and urinary nitrates and nitrites (P-NOx, U-NOx) were compared among normal weight, overweight and obese groups, according to WHO BMI z-score reference. U-Isop were increased in the obese group, whereas U-NOx were increased in both overweight and obese children. U-Isop were positively correlated with U-H2O2, myeloperoxidase (MPO), high-sensitivity C-reactive protein, HOMA-IR and TAG. TAS correlated negatively with U-Isop and MPO and positively with PWV. HOMA-IR and U-H2O2 were associated with higher U-Isop, independently of BMI and eGFR, and total cholesterol and U-H2O2 were associated with U-NOx, independently of BMI, eGFR values and P-NOx concentration. In overweight and obese children, eGFR decreased across P-NOx tertiles (median: 139·3 (25th, 75th percentile 128·0, 146·5), 128·0 (25th, 75th percentile 121·5, 140·4), 129·5 (25th, 75th percentile 119·4, 138·3), P for linear trend=0·003). We conclude that oxidant status and NO are increased in relation to fat accumulation and, even in young children, they translate into higher values of cardiometabolic risk markers and affect renal function.