Prehypertension and Endothelial Dysfunction: The Role of Oxidative Stress

Prehypertension, defined as blood pressure of 120–139/80–89 mmHg, affects approximately 36–38% of adults worldwide and is associated with a substantially increased risk of cardiovascular disease, stroke, and coronary heart disease. Beyond being a transitional stage toward overt hypertension, prehypertension represents a biologically active vascular state in which early vascular injury is already evident. Endothelial dysfunction is considered the earliest detectable vascular abnormality in prehypertension and is characterized by reduced nitric oxide bioavailability, endothelial nitric oxide synthase (eNOS) uncoupling, and increased asymmetric dimethylarginine levels. These alterations are accompanied by endothelial activation, reflected by enhanced expression of adhesion molecules and endothelin-1, as well as impaired endothelial progenitor cell function with a reported threshold effect at systolic blood pressure of 130 mmHg. In parallel, prehypertensive individuals exhibit increased arterial stiffness and microvascular abnormalities, including systemic capillary rarefaction and retinal microvascular alterations. Oxidative stress, driven mainly by NADPH oxidase activation and eNOS uncoupling, appears to be a central mechanism linking elevated blood pressure with endothelial dysfunction and progressive vascular damage. However, the temporal relationship between oxidative imbalance, endothelial dysfunction, and blood pressure progression remains unclear. It is still uncertain whether oxidative stress initiates vascular impairment or primarily accelerates already established endothelial injury. Further prospective studies are needed to define the vascular trajectory of prehypertension, clarify its prognostic relevance, and identify whether early vascular alterations represent therapeutic targets for cardiovascular prevention. By integrating current evidence, this review examines endothelial dysfunction in prehypertension, with particular attention to oxidative stress and its interactions with NO signaling, endothelial activation, and vascular remodeling.