Histological and in vitro studies supporting decreased uteroplacental blood flow as explanation for XXXX after administration of vasodilators.

@entity154 @entity137 @entity548 @entity10202 @entity4 @entity2514 @entity95 @entity9805 @entity1573 @entity397 @entity594
In a recent study, the vasodilating drugs @entity594 , @entity9805 , @entity10202 , and @entity2514 induced @entity154 in @entity95 , when given on day 16 of pregnancy. Histologically, the changes were characterized by disturbed chondrogenesis. In order to elucidate mechanisms behind the defects, the fetal concentration of @entity10202 was measured, and the fetal limb plates were examined histologically, at 0, 2, 4, 8, 12, and 24 hours after single oral administration of @entity10202 (12 mumol/kg) on day 16 in pregnant @entity95 . The effects of @entity594 , @entity9805 , and @entity10202 were also investigated in an in vitro system, in which @entity1573 embryonic mesenchymal limb bud cells differentiated into chondrocytes. In this system, no inhibition of chondrogenesis was observed below concentrations 3 x 10(5) M. At this concentration, unspecific @entity137 was found. The highest fetal concentrations of @entity10202 were more than 500 times lower than what was required for in vitro @entity137 . Histologically, the digital areas of the limb plates showed extensive @entity4 and dilatation of marginal sinus within 2 hours. After 8 hours, @entity397 of the thin-walled vessels occurred with @entity548 . Finally, small necroses and blisters were observed. Similar early changes have been reported in experiments where @entity154 were induced by clamping uterine vessels. This study thus indicates that the @entity154 after administration of high doses of vasodilators are secondary to pharmacological action (associated with a significant reduction in the uteroplacental blood flow), and not a direct effect on fetal chondrogenesis.
