High-salt diet intake-induced endothelial dysfunction is associated with vascular senescence

Excessive salt intake, commonly exceeding recommended limits, is strongly associated with cardiovascular risks, including endothelial dysfunction and hypertension. While the impact of high salt consumption on blood pressure is well-documented, the vascular mechanisms remain unclear. Cellular senescence – a state of stable growth arrest accompanied by phenotypic changes, including a proinflammatory secretome – impairs vascular function by reducing nitric oxide (NO) bioavailability. However, it is uncertain whether a high-salt (HS) diet induces endothelial dysfunction by triggering endothelial senescence. To investigate whether an HS diet induces endothelial dysfunction and senescence, male C57BL6 mice were treated with HS (8% sodium chloride) for 14 days (HS14) or 28 days (HS28), with a control group fed a standard diet (0.5% sodium chloride, HS0). Using wire myograph, we identified endothelial dysfunction in mesenteric arteries in the HS28 group, characterized by impaired relaxation to acetylcholine (ACh), but not in HS14 [Maximal relaxation (%): HS0: 97±2, HS14: 98±2, HS28: 81±2, p=0.8950 and p=0.0007 vs HS0, respectively]. Western blot analysis of senescence markers (p21, p16, and p53) revealed increased p16 expression in aortas from HS14, whereas p21 and p53 were upregulated in aortas from HS28. Since senescence affects NO bioavailability, we further evaluated ACh responses in the presence of L-NAME (1 µM), which affected the vasodilation in both HS groups [Maximal relaxation (%): HS0: 81±4, HS14: 54±6, HS28: 56±5, p=0.01 and p=0.01 vs HS0, respectively], suggesting an NO-dependent mechanism. These findings suggest that HS intake promotes endothelial dysfunction and potentially elevates cardiovascular risk by inducing endothelial senescence. Further studies are needed to determine whether hypertension associated with HS consumption is mediated by this mechanism. R01-HL169202-01 and R00-HL14013903 to TB This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.