Cardiovascular Response of Rat Aorta to Di-(2-ethylhexyl) Phthalate (DEHP) Exposure

Cardiovasc Toxicol. 2018 Aug;18(4):356-364. doi: 10.1007/s12012-017-9439-6.


Phthalates are one of the main constituents of plastic, reaching up to 40% of the total plastic weight, and their main function is to impart flexibility/elasticity to polymers that would otherwise be rigid. Phthalates are known as endocrine disruptors, since they can interfere with hormone homeostasis. Regarding the cardiovascular system, it was already shown the effects of di-(2-ethylhexyl) phthalate (DEHP) exposure with significant changes in several calcium-handling proteins and an increase in the blood pressure of mice offspring, suggesting that DEHP leads to vasocontraction. However, the mechanisms involved were not elucidated yet. The aim of this study is to analyse the involvement of calcium channels in the effects induced by DEHP on vascular smooth muscle cells. Endothelium-denuded aorta artery rings were prepared from male Wistar rats and incubated in an organ bath, and the whole-cell configuration of Patch Clamp technique was used to measure the activity of L-type Ca2+ channels (LTCC) in A7r5 cells. Overall, DEHP caused relaxation on KCl-induced contraction at higher concentrations and inhibited the basal and BAY K8644-stimulated calcium current, indicating that this drug blocks LTCC. These results suggest that DEHP induces relaxation on vascular smooth muscle cells due to the inhibition of calcium channels.

Keywords: A7r5 cells; Calcium channels; Di-(2-ethylhexyl) phthalate; Rat aorta; Vasorelaxation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aorta / drug effects
  • Aorta / metabolism
  • Calcium Channel Blockers / toxicity*
  • Calcium Channels, L-Type / drug effects*
  • Calcium Channels, L-Type / metabolism
  • Calcium Signaling / drug effects
  • Cell Line
  • Diethylhexyl Phthalate / toxicity*
  • Dose-Response Relationship, Drug
  • In Vitro Techniques
  • Male
  • Membrane Potentials
  • Muscle, Smooth, Vascular / drug effects*
  • Muscle, Smooth, Vascular / metabolism
  • Myocytes, Smooth Muscle / drug effects*
  • Myocytes, Smooth Muscle / metabolism
  • Plasticizers / toxicity*
  • Rats, Wistar
  • Vasodilation / drug effects*


  • Calcium Channel Blockers
  • Calcium Channels, L-Type
  • Plasticizers
  • Diethylhexyl Phthalate