Related Experiment Videos
Cardiovascular alterations in rat fetuses exposed to calcium channel blockers
W J Scott1, E Resnick, H Hummler
1Division of Developmental Biology, Children's Hospital Research Foundation, Cincinnati, OH 45229-3039, USA.
Abstract:
Preclinical toxicologic investigation suggested that a new calcium channel blocker, Ro 40-5967, induced cardiovascular alterations in rat fetuses exposed to this agent during organogenesis. The present study was designed to investigate the hypothesis that calcium channel blockers in general induce cardiovascular malformations indicating a pharmacologic class effect. We studied three calcium channel blockers of different structure, nifedipine, diltiazem, and verapamil, along with the new agent. Pregnant rats were administered one of these calcium channel blockers during the period of cardiac morphogenesis and the offspring examined on day 20 of gestation for cardiovascular malformations. A low incidence of cardiovascular malformations was observed after exposure to each of the four calcium channel blockers, but this incidence was statistically significant only for verapamil and nifedipine. All four agents were associated with aortic arch branching variants, although significantly increased only for Ro 40-5967 and verapamil.
Insights
This study investigated if calcium channel blockers cause fetal heart defects. Some blockers, like verapamil and nifedipine, showed a significant increase in cardiovascular malformations in rat fetuses.
Area of Science:
- Pharmacology
- Developmental Toxicology
- Teratology
Background:
- Preclinical studies indicated Ro 40-5967, a novel calcium channel blocker, may cause fetal cardiovascular alterations.
- Calcium channel blockers are widely prescribed, necessitating an understanding of their potential teratogenic effects.
Purpose of the Study:
- To determine if calcium channel blockers as a class induce cardiovascular malformations in developing fetuses.
- To investigate a potential pharmacologic class effect of cardiovascular malformations associated with calcium channel blockers.
Main Methods:
- Pregnant rats were administered four different calcium channel blockers (Ro 40-5967, nifedipine, diltiazem, verapamil) during organogenesis.
- Offspring were examined on day 20 of gestation for the presence of cardiovascular malformations and aortic arch branching variants.
Main Results:
- A low incidence of cardiovascular malformations was observed with all four agents.
- Statistically significant increases in cardiovascular malformations were noted for verapamil and nifedipine.
- Aortic arch branching variants were associated with all agents, significantly increased for Ro 40-5967 and verapamil.
Conclusions:
- Calcium channel blockers may pose a risk for inducing cardiovascular malformations during fetal development.
- Verapamil and nifedipine demonstrated a statistically significant teratogenic effect on the fetal cardiovascular system in rats.
- Further research is warranted to fully elucidate the teratogenic potential of this drug class.