Effects of tributyltin exposure on endothelium-dependent coronary vasodilation in female rats

Introduction: Tributyltin (TBT) is an environmental contaminant associated with several toxic effects, including cardiovascular alterations. However, its impact on coronary vascular function remains poorly understood. This study investigated the effects of low-dose TBT exposure on coronary endothelial function and vascular morphology in female rats.

Methods: Female rats were treated daily for 15 days with vehicle (control group) or TBT (100 ng/kg/day). Estrous cyclicity was monitored throughout the experimental period. Coronary vascular reactivity was evaluated in isolated hearts using the Langendorff technique by constructing concentration–response curves to bradykinin (0.1–1000 nM, bolus injection). Baseline coronary perfusion pressure (CPP) was measured before pharmacological interventions. Bradykinin-induced relaxation was analyzed under control conditions and after infusion of L-NAME, indomethacin, or clotrimazole to investigate the participation of nitric oxide (NO), cyclooxygenase, and cytochrome P450 pathways, respectively. Coronary artery morphology was assessed by hematoxylin and eosin staining.

Results: Exposure to TBT increased the involvement of the NO pathway in endothelium-dependent coronary relaxation. In parallel, coronary arteries from TBT-treated rats exhibited structural alterations characterized by reduced tunica media thickness and signs of smooth muscle cell atrophy. Additionally, TBT exposure disrupted the estrous cycle and promoted histological alterations in reproductive tissues, including changes in endometrial, myometrial, and luminal epithelial thickness.

Conclusion: These findings demonstrate that subacute exposure to low-dose TBT induces important cardiovascular and reproductive alterations in female rats, suggesting that even doses below currently accepted safety limits may represent a potential cardiovascular risk factor.