Pathophysiological Mechanisms and Clinical Controversies of Sodium-Induced Hypertension: A Multi-Systemic Perspective

Hypertension remains the primary modifiable driver of global cardiovascular morbidity, yet the long-standing paradigm of universal sodium restriction is increasingly challenged by the intricate biological heterogeneity of salt sensitivity. This review elucidates the evolving pathophysiological landscape of sodium-induced hypertension, transcending the classical Guytonian pressure-natriuresis model to incorporate emerging evidence of endothelial glycocalyx degradation, non-osmotic interstitial sodium sequestration, and gut-immune axis dysregulation. Furthermore, we critically interrogate the epidemiological "salt controversy," examining how methodological artifacts-specifically the systematic biases inherent in spot urine sampling-may contribute to the observed J-shaped associations between sodium intake and clinical outcomes. By integrating the modulatory role of the dietary sodium-to-potassium ratio and the genetic/epigenetic determinants of individual salt-sensitive phenotypes, we propose a paradigmatic shift toward a precision nutrition approach.