Recent advances in the role of mechanical signal transduction in hypertension

Hypertension is a major risk factor for cardiovascular disease and alters the mechanical microenvironment of the vascular wall and target organs. Key mechanical disturbances include disturbed shear stress, excessive circumferential stretch, elevated hydrostatic pressure, and increased extracellular matrix stiffness. These forces are sensed by multiple classes of mechanosensors, including mechanosensitive ion channels, integrin-based adhesion complexes, G protein-coupled receptors, primary cilia, baroreceptor afferents, and nuclear mechanosensing structures. Activation of these sensors engages interconnected Ca²⁺-dependent, RhoA/Rho-associated protein kinase, mitogen-activated protein kinase, phosphoinositide 3-kinase/Akt/endothelial nitric oxide synthase, Yes-associated protein/transcriptional coactivator with PDZ-binding motif, redox-sensitive, inflammatory, and mechano-epigenetic pathways. This review summarizes how altered mechanotransduction may contribute to endothelial dysfunction, vascular smooth muscle cell phenotypic switching, vascular remodeling, and cardiac and renal target-organ injury in hypertension. Mechanotransduction is unlikely to represent a universal initiating cause of hypertension. Rather, it should be viewed as a context-dependent set of adaptive and maladaptive responses that varies according to cell type, vascular bed, mechanical stimulus, disease stage, and experimental model. Physiological mechanotransduction helps maintain vascular homeostasis and baroreflex function, whereas sustained pathological loading may amplify oxidative stress, inflammation, fibrosis, and vascular stiffening. However, most direct mechanistic evidence derives from cultured cells and animal models, and human genetic, tissue, biomarker, and interventional data remain limited. Conventional antihypertensive therapy therefore remains the foundation of clinical management, whereas direct targeting of mechanosensors or downstream mechanotransduction pathways remains experimental and requires stronger human validation.