Hypertension is still the leading cause of death globally, a global problem. Hypertension occurs in one in three adults worldwide. Currently, a new concept has emerged that the process of hypertension starts in the early stages of a person's life.
This concept, based on the observation that the fetus is exposed to adverse conditions during development while in the womb, increases the risk of chronic diseases that occur in the future. This concept is "the developmental origins of health and disease (DOHaD)."
In particular, the DOHaD concept, apart from determining the initial risk for the development of hypertension, also offers a new way to prevent hypertension through reprogramming therapy. By switching from therapy in adulthood to treatment in early life before the onset of the disease, it is hoped to reverse the processes that will lead to hypertension. Thus, the DOHaD concept raises a new hypothesis that early reprogramming therapy has the potential as an innovative strategy for reducing the global burden of hypertension.
A growing body of evidence suggests that oxidative stress is involved in hypertensive disease's developmental origin (DOHaD). Oxidative stress is caused by an imbalance between free radicals (reactive oxygen species/ROS and reactive nitrogen species/RNS) and antioxidants. Experimental studies show that under oxidative stress conditions, there is an imbalance between the production of ROS and NO/nitric oxide (NO is known to act as an antioxidant at the cellular level and acts as a vasodilator). This condition causes an oxidation reaction in the main organs controlled by blood pressure, such as the brain, kidneys, heart, and blood vessels, which underlies the occurrence of hypertension. On the other hand, antioxidant therapy is known to reduce oxidative stress and blood pressure.
A recent review by Tain and Hsu, published in the journal Antioxidants in 2022, evaluated the scientific evidence regarding the interaction between oxidative stress and the process of developing hypertension. This review discusses the role of oxidative stress in the origin of hypertension development and the potential of antioxidant therapy as a new prevention strategy for hypertension.
Under physiological conditions, maintaining normal blood pressure requires the coordinated interaction of several systems, namely the renin-angiotensin system (RAS), natriuretic peptide, sodium excretion, endothelium, and the sympathetic nervous system. Oxidative stress causes dysfunction in blood pressure-controlled organs and remodeling due to oxidative damage and impairs these coordinated regulatory systems, leading to hypertension.
Antioxidants as a Hypertension Reprogramming Strategy
Based on an understanding of the concept of "developmental origins of health and disease (DOHaD)." Therapeutic approaches can be started early, even before hypertension occurs, called reprogramming or reprogramming therapy. Antioxidants improve endothelial function, normalize vascular remodeling, and reduce arterial stiffness. Because oxidative stress plays an essential role in the origin of hypertension development, antioxidant therapy can be considered a reprogramming strategy to prevent the occurrence of hypertension in the future.
There are two groups of antioxidants, namely enzymatic and non-enzymatic antioxidants. Superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase are Enzymatic antioxidants. Non-enzymatic antioxidants are classified as natural and synthetic antioxidants, which can be endogenous and exogenous. Examples of non-enzymatic natural antioxidants are carotenoids, flavonoids, polyphenols, amino acids, melatonin, and vitamins A, C, and E. Examples of non-enzymatic synthetic antioxidants are N-acetylcysteine (NAC). Several natural antioxidants such as amino acids, vitamins, melatonin, and resveratrol (polyphenols) have shown benefits for preventing hypertension.
Clinical studies have shown an association between the patient's antioxidant status and hypertension. Plasma vitamin C levels, for example, are inversely related to blood pressure, and circulating antioxidant capacity is decreased in hypertension. Decreased activity and plasma levels of antioxidant enzymes, including SOD, glutathione peroxidase, and catalase, have also been reported in patients with essential hypertension. Hypertensive patients showed higher plasma levels of H2O2 (hydrogen peroxide/free radicals), and increased markers of oxidative stress in plasma and urine, namely the reactive substance thiobarbituric acid, oxLDL (oxidized low-density lipoprotein), and 8 isoprostanes compared to normotensive individuals. In the Alpha-Tocopherol, Beta Carotene Cancer Prevention Study, a 30-year prospective cohort analysis, it was found that higher baseline serum a-tocopherol levels were associated with a reduced risk of cardiovascular disease and overall death. In addition, a national health and nutrition examination survey from 2007 to 2014 by Li, et al. showed that higher intakes of alpha-carotene, beta carotene, beta-cryptoxanthin, lycopene, and lutein were associated with a lower risk of hypertension.
Although further clinical research is needed, the clinical benefits of antioxidants in preventing hypertension appear to be promising.
Conclusion:
A new concept has emerged regarding "the developmental origins of health and disease (DOHaD) hypertension." This concept provides an understanding that the process of hypertension starts in the early stages of a person's life, even before hypertension occurs. Evidence has shown that oxidative stress is involved in the pathogenesis or origin of the development of hypertension. Therefore, through its role in counteracting free radicals, antioxidants are considered to be able to prevent hypertension in the future. This antioxidant therapeutic approach can even be started before hypertension occurs, called reprogramming therapy. In other words, antioxidant therapy has the potential and promise to be used as a reprogramming strategy to prevent hypertension in the future.
Image: Illustration (Freepik)
Reference:
1.Tain YL, Hsu CN. Oxidative Stress-Induced Hypertension of Developmental Origins: Preventive Aspects of Antioxidant Therapy. Antioxidants (Basel). 2022;11(3):511.
2. Griendling KK, Camargo LL, Rios FJ, Alves-Lopes R, Montezano AC, Touyz RM. Oxidative Stress and Hypertension. Circ Res. 2021;128(7):993-1020.
