Oxidative Stress and Antioxidants in Hypertension: A Review on Mechanisms and Clinical Challenges.

Abstract

Hypertension remains a major global health burden, with many patients exhibiting resistance to standard antihypertensive regimens. Oxidative stress-driven by reactive oxygen species (ROS) generated through the activation of the renin-angiotensin-aldosterone system (RAAS)-is increasingly recognized as a potential contributor to vascular dysfunction, inflammation, and elevated blood pressure. This review aims to synthesize current mechanistic evidence on the role of oxidative stress in hypertension and to evaluate clinical data on whether antioxidant interventions can mitigate hypertension and its associated organ damage. Preclinical and animal studies provide strong support for a causal link between elevated ROS, redox-sensitive signaling, and increased blood pressure, endothelial dysfunction, and end-organ injury. However, clinical trials investigating antioxidant therapies have produced inconsistent results. Differences in antioxidant type, dosage, timing, and study populations likely contribute to this heterogeneity. The discrepancy between robust mechanistic data and equivocal clinical outcomes underscores translational challenges. While oxidative stress appears to play a central role in hypertension pathophysiology, current evidence does not support the routine use of antioxidants as antihypertensive therapy. Future research should focus on welldesigned trials with standardized antioxidant regimens, stratified patient populations, and long-term follow-up to clarify whether targeting redox imbalance can yield meaningful clinical benefits.