Inotropic effect of increasing concentration of Ca2+ in the fetal rat heart with retinoic acid-induced malformations

Pediatr Res. 1995 Dec;38(6):892-5. doi: 10.1203/00006450-199512000-00011.

Abstract

Cardiac malformations (pulmonary trunk stenosis, ventricular septal defect, and double outlet right ventricle) were induced by the administration of two doses of retinoic acid (RA) to Wistar rats on d 13 of pregnancy. Contractile performance of the isolated perfused rat heart and its inotropic response to Ca2+ (0.6-10.0 mmol.L-1) was studied in 20-d-old fetuses. The body weight of RA-exposed fetuses was significantly lower compared with controls. RA negatively influenced the contractile parameters of the fetal rat heart. The most pronounced effect was, except at a Ca2+ concentration of 2.5 mmol.L-1, observed at developed force at all other concentrations. Simultaneously, the sensitivity to Ca2+, expressed as the Ca2+ concentration at which 30% of maximum was attained, ws significantly lower in RA-exposed hearts. This implies that the malformed heart is more dependent on the extracellular sources of Ca2+.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / pharmacology*
  • Drug Evaluation, Preclinical
  • Female
  • Fetal Heart / abnormalities
  • Fetal Heart / drug effects*
  • Fetal Heart / metabolism
  • Myocardial Contraction / drug effects*
  • Pregnancy
  • Rats
  • Rats, Wistar
  • Stimulation, Chemical
  • Tretinoin

Substances

  • Tretinoin
  • Calcium