Effects of Exposure to Tributyltin on Endothelium-Dependent Vasodilation in Mesenteric Resistance Arteries of Wistar Rats

Tributyltin (TBT) is a persistent organic pollutant and endocrine disruptor associated with cardiovascular damage. Although the World Health Organization established an acceptable daily intake (ADI) of 250 ng/kg/day, evidence suggests that even low doses may induce vascular dysfunction. However, the effects of TBT on mesenteric resistance arteries (MRA) remain unclear. This study evaluated the effects of low-dose TBT exposure (100 ng/kg/day) on MRA vascular reactivity. Female Wistar rats (12 weeks old) were divided into two groups: CT — receiving vehicle solution (0.4 % ethanol), and TBT — receiving TBT (100 ng/kg/day), both administered via oral gavage. All experimental protocols were approved by the Institutional Ethics Committee (#19/2022). Mesenteric resistance arteries were isolated and mounted on a wire myograph for vascular reactivity analysis. Concentration-response curves to acetylcholine (ACh, 1 nM–10 μM) were obtained in vessels precontracted with phenylephrine (PE, 3 μM), as well as curves to PE (1 nM–100 μM), before and after incubation with L-NAME (300 μM), indomethacin (10 μM), or clotrimazole (0.75 μM). Data were analyzed using two-way ANOVA followed by Sidak’s post hoc test and Student’s t-test (p < 0.05). TBT exposure did not alter vasodilation (CT: 90.5 ± 2.9 %; TBT: 93.2 ± 3.1 %), but promoted changes in the epoxyeicosatrienoic acid (EET)-mediated relaxation pathway, reducing the maximum response (CT EET: 62.5 ± 6.3 %; TBT EET: 6.7 ± 2.5 %). In the nitric oxide pathway, the presence of TBT modified the maximum response (TBT: 93.2 ± 3.1 %; TBT L-NAME: 74.26 ± 5.5 %), unlike the CT group (CT: 90.6 ± 2.9 %; CT L-NAME: 80.4 ± 6.67 %). The remaining relaxation pathways remained similar. In conclusion, TBT alters vascular mechanisms even at doses below the ADI value.