Early Origins of Hypertension: Should Prevention Start Before Birth Using Natural Antioxidants?

Abstract

Hypertension may originate in early life. Reactive oxygen species (ROS) generated due to the exposure of adverse in utero conditions causes developmental programming of hypertension. These excessive ROS can be antagonized by molecules which are antioxidants. Prenatal use of natural antioxidants may reverse programming processes and prevent hypertension of developmental origin. In the current review, firstly we document data on the impact of oxidative stress in hypertension of developmental origin. This will be followed by effective natural antioxidants uses starting before birth to prevent hypertension of developmental origin in animal models. It will also discuss evidence for the common mechanisms underlying developmental hypertension and beneficial effects of natural antioxidant interventions used as reprogramming strategies. A better understanding of the reprogramming effects of natural antioxidants and their interactions with common mechanisms underlying developmental hypertension is essential. Therefore, pregnant mothers and their children can benefit from natural antioxidant supplementation during pregnancy in order to reduce their risk for hypertension later in life.

Preventing Developmental Origins of Cardiovascular Disease: Hydrogen Sulfide as a Potential Target?

“…Oxidative damage in the heart, kidney, and blood vessels is well-known for its contribution to organ dysfunction and CVD. In the prenatal dexamethasone plus postnatal high-fat diet model, high-fat intake caused hypertension in adult offspring coinciding with reduced renal CBS and 3MST protein levels [62].…”

“…Owing to its low antioxidant capacity, the developing fetus is extremely vulnerable to oxidative damage [55]. As we reviewed elsewhere [6], many maternal insults have been described to induce cardiovascular programming associated with oxidative stress, including undernutrition [56], preeclampsia [57], maternal diabetes [58], maternal exposure to nicotine or ethanol [59,60], maternal high-fat intake [61], and prenatal glucocorticoid or hypoxia exposure [62,63]. Oxidative damage in the heart, kidney, and blood vessels is well-known for its contribution to organ dysfunction and CVD.…”

“…H 2 S has an antioxidant property, by which it is able to scavenge ROS, increase antioxidant glutathione, and activate nuclear factor E2related factor 2 (Nrf2), a transcription factor for protection against oxidative stress [9][10][11]. Additionally, N-acetylcysteine (NAC), a precursor for H 2 S synthesis, has been reported to reprogram hypertension in animal models of developmental hypertension, including suramin-induced preeclampsia [57], and prenatal dexamethasone plus postnatal high-fat diet [62].…”

Developmental Origins of Kidney Disease: Why Oxidative Stress Matters?

“…Renal programming, apart from oxidative stress, has been linked to other common molecular mechanisms [ 2 , 3 , 6 , 8 ]. On the other hand, several beneficial mechanisms have been reported related to the reprogramming effects of perinatal antioxidant therapy on developmental programming [ 21 ], such as activation of nutrient-sensing signals, rebalancing of the renin-angiotensin system (RAS), and reshaping gut microbiota. Therefore, oxidative stress seems not alone lead to renal programming.…”

“…The idea from DOHaD research opens up new avenues to reverse the programming process by early intervention aiming to prevent developmental origins of kidney disease in adulthood via so-called reprogramming [ 10 ]. Animal studies that have been published recently support that maternal antioxidant therapy can work as a reprogramming strategy to prevent hypertension programmed by diverse maternal insults [ 21 ]. Nevertheless, little is known on whether gestational supplementing with antioxidants can be protective on kidney disease programmed by a variety of early-life insults.…”