Hypertension is sustained not only by abnormal vascular tone but also by structural and mechanical remodeling of resistance and conduit arteries. Although innate immune activation is recognized in hypertension, how inflammatory sensing becomes a stable vascular phenotype remains unclear. The NLR family pyrin domain-containing 3 (NLRP3) inflammasome responds to neurohumoral, ionic, metabolic, mitochondrial and mechanical stress signals and may provide this missing link. This review develops a cell-resolved model in which NLRP3 activation in endothelial cells, vascular smooth muscle cells, myeloid cells, adventitial fibroblasts and perivascular adipose tissue coordinates endothelial dysfunction, smooth-muscle phenotypic switching, immune amplification and extracellular-matrix remodeling. In experimental systems, these responses collectively contribute to inward remodeling of resistance arteries, fibrosis, rarefaction and conduit-artery stiffening, which in turn generate mechanical stress, mitochondrial injury, damage-associated molecular patterns and cellular senescence that sustain inflammasome activity. We propose vascular aging as a temporal amplifier of the NLRP3-remodeling feed-forward loop rather than merely a parallel comorbidity. Genetic and pharmacological studies provide causal evidence in selected angiotensin II- and salt/mineralocorticoid-driven experimental models. By contrast, human evidence remains largely associative, and no trial has shown that selective NLRP3 inhibition lowers blood pressure or reverses vascular remodeling in primary hypertension. Early clinical studies demonstrate target engagement. Future trials should enrich for inflammation-active, salt-sensitive, metabolic or early-vascular-aging phenotypes and incorporate arterial stiffness, microvascular structure and target-engagement biomarkers alongside ambulatory blood pressure. This approach may determine whether NLRP3 is a modifiable driver of hypertensive vascular disease or primarily a marker of established injury.
