Bisphenol A decreases atrial contractility involving NO-dependent G-cyclase signaling pathway

J Appl Toxicol. 2011 Oct;31(7):698-702. doi: 10.1002/jat.1647. Epub 2011 Feb 23.

Abstract

Bisphenol A (BPA) is used in manufacturing plastics. Even though BPA is reported to produce reproductive and behavioral toxicity in experimental animals, the direct effect of BPA on the cardiovascular system is not known. The present study was therefore undertaken to evaluate the effect of BPA, on spontaneously beating rat right atrial preparations. In this study, in vitro isometric contractions of right atria were recorded. Cumulative concentration-response of BPA on atrial contractions was obtained in the absence or presence of antagonists. BPA (0.1-100 μ m) decreased the rate and the force of atrial contractions in a concentration-dependent manner. At 100 μ m, the decreases were >90%. The BPA-induced changes were not blocked by atropine (muscarinic receptor blocker). However, pretreatment with N-ω-nitro-L-arginine methyl ester (L-NAME, a nitric oxide synthase inhibitor) or methylene blue (a guanylyl cyclase inhibitor) blocked the BPA-induced changes in rate and force. Nitroglycerine, an NO-donor, decreased the rate and force of atrial contractions. Further, the BPA-induced changes were not due to the solvent (ethanol) used to dissolve it. The present study therefore indicates that BPA decreases the atrial contractility involving NO-dependent G-cyclase signaling mechanisms.

MeSH terms

  • Animals
  • Atropine / pharmacology
  • Benzhydryl Compounds
  • Cardiotoxins / toxicity*
  • Enzyme Inhibitors / pharmacology
  • Guanylate Cyclase / metabolism*
  • Heart Atria / drug effects*
  • Heart Atria / metabolism
  • Methylene Blue / pharmacology
  • Muscle Contraction / drug effects*
  • NG-Nitroarginine Methyl Ester / pharmacology
  • Nitric Oxide / metabolism
  • Nitroglycerin / toxicity
  • Phenols / toxicity*
  • Rats
  • Receptors, Muscarinic / drug effects
  • Receptors, Muscarinic / metabolism
  • Signal Transduction*

Substances

  • Benzhydryl Compounds
  • Cardiotoxins
  • Enzyme Inhibitors
  • Phenols
  • Receptors, Muscarinic
  • Nitric Oxide
  • Atropine
  • Guanylate Cyclase
  • Nitroglycerin
  • bisphenol A
  • Methylene Blue
  • NG-Nitroarginine Methyl Ester