Contents lists available at ScienceDirect Vascular Pharmacology journal homepage: www.elsevier.com/locate/vph Maternal high-sodium intake afects the ofspring’ vascular renin-angiotensin system promoting endothelial dysfunction in rats Juliana Santos-Rocha, Geórgia A. Lima-Leal, Hicla S. Moreira, Fernanda E. Ramos-Alves, Francine G. de Sá, Gloria P. Duarte, Fabiano E. Xavier ⁎ Departamento de Fisiologia e Farmacologia, Universidade Federal de Pernambuco, Recife, Brazil ARTICLEINFO Keywords: Perinatal sodium overload Angiotensin II Cyclooxygenase-2 Oxidative stress Endothelial dysfunction ABSTRACT Perinatal sodium overload induces endothelial dysfunction in adult ofspring, but the underlying mechanisms are not fully known. The involvement of tissue renin-angiotensin system on high sodium-programmed en- dothelial dysfunction was examined. Acetylcholine and angiotensin I and II responses were analyzed in aorta and mesenteric resistance arteries from 24-week-old male ofspring of normal-salt (O-NS, 1.3% NaCl) and high-salt (O-HS, 8% NaCl) fed dams. COX-2 expression, O 2 – production and angiotensin converting enzyme (ACE) activity were determined. A se- parated O-HS was treated with losartan (15mgkg −1 /day) for eight weeks. Compared to O-NS, O-HS were normotensive. Acetylcholine-induced relaxation was impaired in O-HS ar- teries, which was improved by tempol, apocynin or indomethacin. The angiotensin I-induced contraction was greater in O-HS arteries, whereas the angiotensin II responses were unchanged. ACE activity, O 2 – production and COX-2 expression were increased in O-HS arteries. In this group, the increased O 2 – production was inhibited by apocynin or losartan. Chronic losartan decreased COX-2 expression and restored the endothelium-dependent vasodilation in O-HS. Our fndings reiterate that perinatal sodium overload programs endothelial dysfunction in adult ofspring through a blood pressure-independent mechanism. Our results also suggest that vascular angiotensin II is the main mediator of high sodium-programmed endothelial dysfunction, promoting COX-2 expression and oxidative stress. 1. Introduction Sodium is an essential micronutrient that plays an important role in many body processes, such as nerve conduction, muscle contraction, fuid balance and blood pressure. However, sodium consumption has been increasing worldwide and has raised the cardiovascular disorders incidence, including arterial hypertension, myocardial infarction or stroke[1–3].Currently,dailysodiumintakeisinaveragetenfoldhigher than it was the past and has exceeded the estimated physiological needs [4]. For a long time, the associated high-salt consumption deleterious actions had been related merely to the sodium efect on blood pressure. Currently,severalotherefectshavebeendescribed;insomecases,they occur independently of the other common risk factors. For example, in adult animals, regardless of changes in blood pressure, high-salt intake induces myocardial fbrosis, left ventricular hypertrophy and vascular dysfunction and remodeling [1,5–7]. It is widely accepted that maternal dietary intake and nutritional environment during fetal development have long-term implications for ofspring health [8]. Developmental programming of several diseases has been observed in several studies using animal models of maternal micro and macronutrient restriction and excess. For instance, dietary sodium overload during the pregnancy perturbs placental function, alters fetal development, and predisposes ofspring to cardiovascular and renal alterations in adult life. In the experiments of Contreras et al. [9] and Gray et al. [3], ofspring of high-salt diet-fed dams exhibited higherbloodpressurecomparedwithofspringofcontroldiet-feddams. Excessive salt intake during the pregnancy also impairs the ne- phrogenesis, reducing the nephron number [10], produces glomerulo- sclerosis [11], proteinuria and oxidative stress [12] in adult ofspring. Additionally, prenatal salt-exposed ofspring exhibited left ventricular hypertrophy, cardiac dysfunction, increased arterial wall thickness and endothelial dysfunction [3,13–15]. https://doi.org/10.1016/j.vph.2019.02.001 Received 5 November 2018; Received in revised form 17 December 2018; Accepted 17 February 2019 ⁎ Corresponding author at: Departamento de Fisiologia e Farmacologia, Centro de Biociências, Universidade Federal de Pernambuco, Avenida Prof. Moraes Rêgo, Cidade Universitária, 50670-901 Recife, Brazil. E-mail address: fabianoxavier@ufpe.br (F.E. Xavier). Vascular Pharmacology xxx (xxxx) xxx–xxx 1537-1891/ © 2019 Published by Elsevier Inc. Please cite this article as: Juliana Santos-Rocha, et al., Vascular Pharmacology, https://doi.org/10.1016/j.vph.2019.02.001