Low-Dose Tributyltin Exposure Induces Vascular Dysfunction and Oxidative Stress in Resistance Mesenteric Arteries of Wistar Rats

Introduction: Tributyltin (TBT) is a persistent organic pollutant with bioaccumulative potential. Although the tolerable daily intake is 250 ng/kg/day (WHO), recent evidence suggests cardiovascular toxicity at lower doses. This study investigated the functional and histomorphometric effects of low-dose TBT exposure on resistance mesenteric arteries in rats. Methods: Female Wistar rats were exposed orogastrically for 15 days to vehicle (CT) or TBT (100 ng/kg/day). Protocols were approved by the Ethics Committee (#19/2022). Vascular reactivity to phenylephrine (PE, 10⁻⁹–10⁻⁴ M) was assessed via wire myography before and after L-NAME (300 μM) incubation. Collagen area fractions and morphology were quantified via ImageJ/Fiji software after picrosirius red and H&E staining. Oxygen reactive species (ROS) were evaluated by DHE fluorescence. Data were analyzed using two-way ANOVA (vascular reactivity), Student’s t-test (histomorphometry), and one-way ANOVA (ROS), with Sidak’s/Tukey’s post-tests (p < 0.05). Results: TBT induced a leftward shift in the PE contraction curve (pEC50 CT: 5.8 ± 0.1; TBT: 6.2 ± 0.05), indicating increased vascular hypersensitivity. While L-NAME reduced EC50 in the CT group, the TBT group did not show a shift (EC50 6.2 ± 0.05 vs. 6.0 ± 0.14), suggesting impairment in the nitric oxide (NO) pathway. TBT exposure elevated basal ROS levels and increased pro-oxidant responsiveness to angiotensin II (CT: 25.33 ± 4.03 a.u.; TBT: 42.29 ± 3.21 a.u.). Histologically, TBT increased collagen deposition (15.33 ± 1.97 % vs. CT 10.33 ± 0.91%), although lumen and tunica media dimensions remained unchanged. Conclusion: Exposure to TBT below established safety limits triggers early vascular dysfunction characterized by hypersensitivity, impaired NO signaling, and increased oxidative stress and fibrosis. These findings highlight important microvascular alterations, even at levels currently considered safe by international agencies.