Abstract Accumulating evidence indicates that psychological stress (both acute and chronic) affects blood pressure through neuro-hormonal and inflammatory pathways, leading to transient and sustained elevations in arterial pressure. The interaction among the sympathetic nervous system (SNS), hypothalamic–pituitary–adrenal (HPA) axis, and renin–angiotensin system (RAS), along with vascular endothelial and inflammatory changes, represents the physiological foundation linking psychological stress to hypertension. Recent experimental data suggest that heightened physiological reactivity to stress predicts the later development of hypertension and that interventions such as physical exercise and stress management techniques can reduce this reactivity and lower hypertension risk. 1. Physiological Background 1. Sympathetic Activation and Cytokines Under acute stress, the hypothalamus and brainstem activate sympathetic centers, leading to the release of catecholamines (norepinephrine, epinephrine) that increase cardiac output and cause arterial/venous constriction—producing transient blood pressure elevation. Repeated or sustained exposure induces vascular remodeling, endothelial dysfunction, and chronic low-grade inflammation. 2. HPA Axis and Cortisol Stress activates the HPA axis, elevating cortisol levels. Chronic hypercortisolism enhances vascular sensitivity to catecholamines, increases renal sodium reabsorption, and promotes metabolic and inflammatory pathways that sustain elevated blood pressure. 3. Renin–Angiotensin System (RAS) Stress exposure stimulates RAS activity both centrally and peripherally, increasing angiotensin II, which causes vasoconstriction, oxidative stress, and endothelial dysfunction, contributing to long-term hypertension. 4. Allostatic Load Concept “Allostatic load” represents the cumulative burden of repeated or chronic stress on the body’s regulatory systems (SNS, HPA, metabolic). It manifests as measurable biomarkers (high BP, elevated glucose/lipids, inflammation) and correlates with cardiovascular disease risk. 2. Recent Experimental Evidence • Hyper-reactivity to Stress: Meta-analyses show that individuals with exaggerated physiological responses to acute mental stress (greater BP, HR, and cortisol increases) are more likely to develop hypertension later in life. • Daily Life Studies: Ambulatory monitoring demonstrates that periods of psychological stress correlate with transient BP spikes and that associated behaviors (smoking, poor sleep, alcohol intake) act as mediators. • Exercise Interventions: Randomized controlled trials report that aerobic exercise training reduces BP reactivity to stress, suggesting modifiable mechanisms. 3. Conclusion Psychological stress contributes to hypertension via well-defined physiological mechanisms involving sympathetic activation, HPA axis hyperactivity, and RAS stimulation. These lead to endothelial dysfunction, vascular stiffness, and low-grade inflammation. Combining stress reactivity data with allostatic load biomarkers and ambulatory BP measures can identify high-risk individuals and inform preventive strategies. Ban Dhahir Thabbah Al-Mustaqbal University — Ranked First Among Private Universities.