Impact of various forms of vitamin D on endothelial dysfunction triggered by high glucose conditions in Wistar rats

Endothelial dysfunction (ED) is a hallmark of metabolic disturbances such as Metabolic Syndrome (MetS), where oxidative stress and reduced nitric oxide (NO) bioavailability play key roles. High glucose (HG), a major metabolic alteration in MetS, impairs endothelial signaling in large conduit arteries and microvascular beds through shared mechanisms, including excessive reactive oxygen species (ROS) production and altered endothelial nitric oxide synthase (eNOS) activity.

This study investigated HG-induced ED in rat thoracic aorta and examined the effects of different vitamin D forms on vascular reactivity under HG conditions.

Thoracic aortas from twelve-week-old male Wistar rats were incubated under normal glucose (NG, 11.1 mM) or HG (44.4 mM) conditions for 3 h and treated with tempol (10^-3 M), cholecalciferol (VD1; 10^-5 M), calcidiol (VD2; 10^-6 M), or calcitriol (VD3; 10^-7 M). Endothelium-dependent vasorelaxation was assessed using cumulative concentration-response curves (CCRCs) to acetylcholine (Ach; 10^-9 to 3.10^-5 M); vasoconstriction was evaluated using phenylephrine (Phe; 10^-9 to 3.10^-5 M).

HG impaired ACh-mediated vasorelaxation and increased Phe-induced vasoconstriction. Tempol fully restored endothelial function under HG conditions, confirming the predominant role of oxidative stress. Both cholecalciferol and calcitriol improved ACh-mediated vasorelaxation (pD₂ and E_max) toward NG levels and reduced α₁-adrenergic hyperresponsiveness, although not significantly. Calcidiol showed no significant effect.

Cholecalciferol and calcitriol counteract HG-induced endothelial dysfunction in rat aorta, suggesting that specific vitamin D forms modulate endothelial signaling pathways disrupted in metabolic disturbances. These findings support their therapeutic potential in restoring vascular homeostasis in HG conditions.