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.