Ridogrel improves maternal/fetal homeostasis in an ovine model of pregnancy-induced hypertension.
The effects of ridogrel (a thromboxane synthetase inhibitor/endoperoxide receptor antagonist) were assessed in an ovine model of pregnancy-induced hypertension. Maternal serum prostacyclin and thromboxane levels were quanitiated using RIA, and maternal and neonatal coagulation status was assessed. Pregnancy and neonatal outcome were recorded. Ridogrel, (E)-5-[[[3-pyridinyl)[3-(trifluoromethyl)phenyl]methylen]amin++ +] oxy]pentanoic acid, was administered in one bolus dose at 0.1 or 1.0 mg/kg IV, three hours following the onset of a 27 hour magnesium sulfate infusion given hypertensive ewes to prevent maternal seizures. At both doses, ridogrel improved neonatal outcome (0% neonatal mortality in each ridogrel group versus 67% neonatal mortality in the magnesium sulfate group), and ridogrel at 0.1 mg/kg IV normalized birth weights. Abnormalities of maternal platelet function (abnormal or no response to collagen), occurring during the ovine syndrome, resolved following ridogrel treatment. Ridogrel's effects on maternal and neonatal coagulation were more dramatic at the 0.1 mg/kg IV dose. Ridogrel appeared to be beneficial in this model of pregnancy-induced hypertension.
Keith
J C
JC
Department of Biomedical Sciences, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg 24061.
Endo
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Warwick
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Keith
K E
KE
Brugh
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Rowles
T K
TK
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D005333:Fetus / Q000502:physiology*; D006706:Homeostasis / Q000187:drug effects*; D006973:Hypertension / Q000188:drug therapy*; D010421:Pentanoic Acids / Q000494:pharmacology / Q000627:therapeutic use*; D010919:Placebos; D011247:Pregnancy; D011249:Pregnancy Complications, Cardiovascular / Q000188:drug therapy*; D011725:Pyridines / Q000494:pharmacology / Q000627:therapeutic use*; D011863:Radioimmunoassay; D012756:Sheep; D013929:Thromboxane B2 / Q000097:blood; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*
D010421:Pentanoic Acids; D010919:Placebos; D011725:Pyridines; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D013930:Thromboxane-A Synthase; C060219:ridogrel