Maternal protein restriction induced‐hypertension is associated to oxidative disruption at transcriptional and functional levels in the medulla oblongata

Abstract

Maternal protein restriction during pregnancy and lactation predisposes the adult offspring to sympathetic overactivity and arterial hypertension. Although the underlying mechanisms are poorly understood, dysregulation of the oxidative balance has been proposed as a putative trigger of neural-induced hypertension. The aim of the study was to evaluate the association between the oxidative status at transcriptional and functional levels in the medulla oblongata and maternal protein restriction induced-hypertension. Wistar rat dams were fed a control (normal protein; 17% protein) or a low protein ((Lp); 8% protein) diet during pregnancy and lactation, and male offspring was studied at 90 days of age. Direct measurements of baseline arterial blood pressure (ABP) and heart rate (HR) were recorded in awakened offspring. In addition, quantitative RT-PCR was used to assess the mRNA expression of superoxide dismutase 1 (SOD1) and 2 (SOD2), catalase (CAT), glutathione peroxidase (GPx), Glutamatergic receptors (Grin1, Gria1 and Grm1) and GABA(A)-receptor-associated protein like 1 (Gabarapl1). Malondialdehyde (MDA) levels, CAT and SOD activities were examined in ventral and dorsal medulla. Lp rats exhibited higher ABP. The mRNA expression levels of SOD2, GPx and Gabarapl1 were down regulated in medullary tissue of Lp rats (P<.05, t test). In addition, we observed that higher MDA levels were associated to decreased SOD (approximately 45%) and CAT (approximately 50%) activities in ventral medulla. Taken together, our data suggest that maternal protein restriction induced-hypertension is associated with medullary oxidative dysfunction at transcriptional level and with impaired antioxidant capacity in the ventral medulla.

Effects of high-fat diet on somatic growth, metabolic parameters and function of peritoneal macrophages of young rats submitted to a maternal low-protein diet

“…At the end of lactation, it was observed that prolonged consumption of a LP diet resulted in low body weight and FC in LP dams, despite a similar energy intake and trend in reduced food intake. It is well established that LP intake, reduced FC and body weight gain during pregnancy/lactation are the three main factors influencing maternal and infant outcomes (31)(32)(33) . In fact, we have demonstrated that protein restriction during gestation produces intra-uterine growth restriction and continued protein restriction during lactation counteracts catch up growth and results in long-term decreases in body weight due to a reduction in both lean and fat mass (2,33,34) .…”

Maternal protein malnutrition induced‐hypertension: New evidence about the autonomic and respiratory dysfunctions and epigenetic mechanisms

“…In the same experimental model, Brito‐Alves et al revealed that maternal protein restriction induced‐hypertension is associated with medullary oxidative dysfunction at the transcriptional level (downregulation in antioxidant enzymes, such superoxide dismutase 2 and glutathione peroxidase) and with impaired antioxidant capacity in the ventral medulla. This area has neuronal network involved in the control of sympathetic nervous activity . Thus, it is possible that central and peripheral oxidative imbalance, at least in part, plays a key role in the increase of sympathetic activity and development of AH in protein‐restricted rats.…”

“…There are reports of increased lipid peroxidation and decreased activity of several antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase activities), as well as elements of the GSH system, in the adult brainstem . In the same experimental model, Brito‐Alves et al revealed that maternal protein restriction induced‐hypertension is associated with medullary oxidative dysfunction at the transcriptional level (downregulation in antioxidant enzymes, such superoxide dismutase 2 and glutathione peroxidase) and with impaired antioxidant capacity in the ventral medulla. This area has neuronal network involved in the control of sympathetic nervous activity .…”

Primary Pediatric Hypertension: Current Understanding and Emerging Concepts

“…The cardiac dysfunction may be restricted to the male rat offspring [53]. Maternal protein restriction leads to sympathetic overactivity and oxidative dysfunction at the medulla oblongata of Wistar rat dams [54]. There is an increase in circulating leptin in the adult offspring [55]; leptin can stimulate the sympathetic nervous system in rodents [56•].…”