Tributyltin Affects Rat Vascular Contractility Through L-Type Calcium Channels

  • J. Feiteiro
  • M. Mariana
  • I. Verde
  • E. Cairrão
Research paper


The humans being exposed to tributyltin (TBT), through the ingestion of contaminated diet, particularly seafood, and through the ingestion of indoor dust. TBT is one of the most studied organotins and some reports demonstrated that this compound interferes with the physiology of the cardiovascular system; however, the exact mechanisms involved are still under discussion. Hence, this study aims to evaluate the effects of TBT on the vascular function. The evaluation of TBT effects on the contractility of rat aorta was performed using the organ bath technique using two different contractile agents: noradrenaline (NA) and potassium chloride (KCl). The whole-cell configuration of the patch clamp technique was performed to evaluate the TBT effects on the calcium currents of A7r5 cell line. The results demonstrate that TBT interferes with the vascular system as it elicits relaxation of the rat aorta contracted by NA or by KCl and inhibits L-type calcium currents in smooth muscle cells.


TBT Cardiotoxicity Rat aorta A7r5 Patch clamp Organ bath 



This investigation was supported by FEDER funds through the POCI—COMPETE 2020—Operational Programme Competitiveness and Internationalization in Axis I—Strengthening research, technological development and innovation (Project POCI-01-0145-FEDER-007491) and National Funds by FCT—Foundation for Science and Technology (Project UID/Multi/00709/2013). This work is also supported by the grant: SFRH/BD/131665/2017.

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflicts of interest.


  1. Alvarez E, Cairrão E, Morgado M. Morais C, Verde I (2010) Testosterone and cholesterol vasodilation of rat aorta involves L-type calcium channel inhibition. Adv Pharmacol Sci. Article ID 534184, 10 p.
  2. Botelho G, Bernardini C, Zannoni A, Ventrella V, Bacci ML, Forni M (2015) Effect of tributyltin on mammalian endothelial cell integrity. Comp Biochem Physiol Part—C Toxicol Pharmacol 176–177:79–86. CrossRefGoogle Scholar
  3. Cairrão E, Alvarez E, Carvas JM, Santos-Silva AJ, Verde I (2012) Non-genomic vasorelaxant effects of 17β-estradiol and progesterone in rat aorta are mediated by L-type Ca2+ current inhibition. Acta Pharmacol Sin 33:615–624. CrossRefGoogle Scholar
  4. Cameron JA, Kodavanti PRS, Pentyala SN, Desaiah D (1991) Triorganotin inhibition of rat cardiac adenosine triphosphatases and catecholamine binding. J Appl Toxicol 11:403–409. CrossRefGoogle Scholar
  5. Carre G, Ouedraogo M, Magaud C, Carreyre H, Becq F, Bois P, Supuran CT, Thibaudeau S, Vandebrouck C, Bescond J (2015) Vasorelaxation induced by dodoneine is mediated by calcium channels blockade and carbonic anhydrase inhibition on vascular smooth muscle cells. J Ethnopharmacol 169:8–17. CrossRefGoogle Scholar
  6. dos Santos RL, Podratz PL, Sena GC, Filho VSD, Lopes PFI, Gonçalves WL, Alves LM, Samoto VY, Takiya CM, Miguel EC, Moysés MR, Graceli JB (2012) Tributyltin impairs the coronary vasodilation induced by 17β-estradiol in isolated rat heart. J Toxicol Environ Health A 75(16–17):948–959. CrossRefGoogle Scholar
  7. Fagin D (2012) The learning curve. Nature 490(7421):462–465. CrossRefGoogle Scholar
  8. Fromme H, Mattulat A, Lahrz T, Rüden H (2005) Occurrence of organotin compounds in house dust in Berlin (Germany). Chemosphere 58(10):1377–1383. CrossRefGoogle Scholar
  9. Hendriksen PJM, Schmeits PCJ, Van Loveren H, Shao J, Peijnenburg AA (2014) Mode of action of organotins in immune cells. In: Corsini E, Van Loveren H (eds) Molecular immunotoxicology. Wiley-VCH Verlag GmbH & Co, Weinheim, pp 307–326Google Scholar
  10. Hofmann F, Klugbauer N (1996) Molecular biology and expression of smooth muscle L-type calcium. In: Báránym M (ed) Biochemistry of smooth muscle contraction. Academic, London, pp 221–226CrossRefGoogle Scholar
  11. Jackson WF (2000) Ion channels and vascular tone. Hypertension 35(1):173–178. CrossRefGoogle Scholar
  12. Kannan K, Takahashi S, Fujiwara N, Mizukawa H, Tanabe S (2010) Organotin compounds, including butyltins and octyltins, in house dust from Albany, New York, USA. Arch Environ Contam Toxicol 58(4):901–907. CrossRefGoogle Scholar
  13. Karaki H, Ozaki H, Hori M, Mitsui-Saito M, Amano KI, Harada KI, Miyamoto S, Nakazawa H, Won KJ, Sato K (1997) Calcium movements, distribution, and functions in smooth muscle. Pharmacol Rev 49(2):157–230Google Scholar
  14. Mitra S, Gera R, Siddiqui WA, Khandelwal S (2013) Tributyltin induces oxidative damage, inflammation and apoptosis via disturbance in blood–brain barrier and metal homeostasis in cerebral cortex of rat brain: an in vivo and in vitro study. Toxicology 310:39–52. CrossRefGoogle Scholar
  15. Mizuhashi S, Ikegaya Y (2000) Pharmacological property of tributyltin in vivo and in vitro. Environ Toxicol Pharmacol 8(3):205–212. CrossRefGoogle Scholar
  16. Nath M (2008) Toxicity and the cardiovascular activity of organotin compounds: a review. Appl Organomet Chem 22(10):598–612CrossRefGoogle Scholar
  17. Pereira-Fernandes A, Vanparys C, Tine LMH, Vergauwen L, Knapen D, Jorens PG, Blust R (2013) Unraveling the mode of action of an obesogen: mechanistic analysis of the model obesogen tributyltin in the 3T3-L1 cell line. Mol Cell Endocrinol 370(1–2):52–64. CrossRefGoogle Scholar
  18. Perusquia M, Hernández R, Morales MA, Campos MG, Villalón CM (1996) Role of endothelium in the vasodilating effect of progestins and androgens on the rat thoracic aorta. Gen Pharmacol Vasc S 27(1):181–185. CrossRefGoogle Scholar
  19. Risk & Policy Analysts Limited (RPA) (2005) Risk assessment studies on targeted consumer applications of certain organotin compounds. Final Report, prepared for the European Commission, September 2005.
  20. Rodrigues SML, Ximenes CF, de Batista PR, Simões FV, Coser PHP, Sena GC, Podratz PL, de Souza LNG, Vassallo DV, Graceli JB, Stefanon I (2014) Tributyltin contributes in reducing the vascular reactivity to phenylephrine in isolated aortic rings from female rats. Toxicol Lett 225(3):378–385. CrossRefGoogle Scholar
  21. Scientific Committee on Health and Environmental Risks (SCHER) (2006) Revised assessment of the risks to health and the environment associated with the use of the four organotin compounds TBT, DBT, DOT and TPT. Health and Consumer Protection Directorate. European Commission, EC, p. 27.
  22. Sousa ACA, Pastorinho MR, Takahashi S, Tanabe S (2014) History on organotin compounds, from snails to humans. Environ Chem Lett 12(1):117–137. CrossRefGoogle Scholar
  23. Sousa ACA, Coelho SD, Pastorinho MR, Taborda-Barata L, Nogueira AJA, Isobe T, Kunisue T, Takahashi S, Tanabe S (2017) Levels of TBT and other selected organotin compounds in duplicate diet samples. Sci Total Environ 574:19–23. CrossRefGoogle Scholar
  24. Vanhoutte P, Rimele T (1982) Calcium and [alpha]-adrenoceptors in activation of vascular smooth muscle. J Cardiovasc Pharmacol 4:S287CrossRefGoogle Scholar
  25. Zang W-J, Zacharia J, Lamont C, Wier WG (2006) Sympathetically evoked Ca2+ signaling in arterial smooth muscle. Acta Pharmacol Sin 27(12):1515–1525. CrossRefGoogle Scholar

Copyright information

© University of Tehran 2018

Authors and Affiliations

  1. 1.CICS-UBI—Centro de Investigação em Ciências da SaúdeUniversidade da Beira InteriorCovilhãPortugal

Personalised recommendations