The Future Challenge of Reactive Oxygen Species (ROS) in Hypertension: From Bench to Bed Side

Abstract

Reactive oxygen species (ROS) act as signaling molecules that control physiological processes, including cell adaptation to stress. Redox signaling via ROS has quite recently become the focus of much attention in numerous pathological contexts, including neurodegenerative diseases, kidney and cardiovascular disease. Imbalance in ROS formation and degradation has also been implicated in essential hypertension. Essential hypertension is characterized by multiple genetic and environmental factors which do not completely explain its associated risk factors. Thereby, even if advances in therapy have led to a significant reduction in hypertension-associated complications, to interfere with the unbalance of redox signals might represent an additional therapeutic challenge. The decrease of nitric oxide (NO) levels, the antioxidant activity commonly found in preclinical models of hypertension and the ability of antioxidant approaches to reduce ROS levels have spurred clinicians to investigate the contribution of ROS in humans. Indeed, particular effort has recently been devoted to understanding how redox signaling may contribute to vascular pathobiology in human hypertension. However, although biomarkers of oxidative stress have been found to positively correlate with blood pressure in preclinical model of hypertension, human data are less convincing. We herein provide an overview of the most relevant mechanisms via which oxidative stress might contribute to the pathophysiology of essential hypertension. Moreover, alternative approaches, which are directed towards improving antioxidant machinery and/or interfering with ROS production, are also discussed.

Oxidative stress in chronic kidney disease

“…In contrast to the data on CKD progression, data on the role of OS in CVD focused not only on surrogate outcomes but also on cardiovascular events and mortality. Interestingly, this does not account only for the CKD but also, at least in part, for the general population with preserved kidney function [27,142,143]. Of note, conventional treatments of CVD, including HMGCoA reductase inhibitors (statins), angiotensin-converting enzyme (ACE) inhibitors, and AT1receptor blockers, are all reported to reduce OS in vasculature thereby improving endothelial function and slowing down CVD progression [144,145].…”

Role of Mitophagy in Cardiovascular Disease

“…ROS regulate vascular structure and tension remodeling. An increase or retention of ROS may cause vasoconstriction, decrease vascular diastolic function, damage smooth muscle cells, promote vascular inflammation and remodeling, increase peripheral vascular resistance, and aggravate hypertension [136]. Mfn1, Mfn2, and OPA1 (optic atrophy 1) mRNA levels, which are associated with mitochondrial dynamics, were decreased in hypertensive rat heart models.…”

Health relevance of antihypertensive peptides in foods

“…Moreover, ROS stimulate the production of cytokines that generate over-expressed inflammatory responses. Therefore, peptides showing antiinflammatory and antioxidant activities may also exert lowering BP effects due to the increased bioavailability of NO through the control of cytokine levels and the scavenging of free radicals, respectively [15,16]. Additionally, binding of peptides to opioid receptors can exert lowering effects on BP due to the release of the vasodilator NO or the decreased SNS activity.…”