Background: Essential hypertension is a complex, multifactorial clinical syndrome fundamentally characterized by the persistent hyperactivation of the sympathoadrenal system. This profound autonomic dysregulation contributes not only to the chronic elevation of systemic arterial blood pressure but also plays a central pathogenic role in the progression of hypertensive vasculopathy, insidious target organ damage, and long-term cardiovascular morbidity. β-adrenergic receptor antagonists, universally recognized as β-blockers, have been extensively utilized for several decades to mitigate these deleterious neurohumoral effects. However, the exact pharmacological modulation of the sympathoadrenal system varies significantly and is profoundly dependent upon the specific generation and receptor selectivity of the applied β-blocker. Objective: This comprehensive narrative review aims to meticulously analyze the specific features of sympathoadrenal functional activity in patients with essential hypertension undergoing various regimens of β-blocker therapy, elucidating the intricate neurohumoral, hemodynamic, and metabolic crosstalk that ultimately defines long-term clinical outcomes. Methods: An exhaustive, detailed synthesis of current biomedical literature was conducted, focusing sharply on the differential, generation-specific impacts of first-, second-, and third-generation β-blockers on systemic and regional sympathetic nerve activity, heart rate variability, baroreflex sensitivity, catecholamine spillover kinetics, and critical metabolic parameters. Results: The synthesized evidence demonstrates that while traditional, strictly β₁-selective agents successfully lower systemic blood pressure and blunt chronotropic responses, they frequently fail to reverse the underlying sympathetic central overdrive, leading to a documented phenomenon known as residual sympathetic activation. Conversely, third-generation agents, which possess adjunctive vasodilatory properties mediated through nitric oxide release (e.g., nebivolol) or concurrent -adrenergic blockade (e.g., carvedilol), demonstrate a vastly superior physiological ability to restore sympathovagal balance. These modern pleiotropic agents actively decrease regional norepinephrine spillover, enhance parasympathetic vagal rebound, and significantly improve endothelial function and myocardial energy metabolism. Conclusion: The pharmacological modulation of the sympathoadrenal system extends far beyond the simple, mechanical reduction of heart rate and cardiac output. Selecting the optimal β-blocker in the clinical management of essential hypertension necessitates a highly nuanced, individualized understanding of the drug's specific interactions with central sympathetic outflow, peripheral efferent nerve traffic, and cellular metabolic pathways in order to effectively minimize the persistent burden of residual cardiovascular risk.

Essential hypertension, sympathoadrenal system, β-blockers, heart rate variability, norepinephrine spillover, muscle sympathetic nerve activity, residual cardiovascular risk, autonomic nervous system, carvedilol, nebivolol.

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