Effects of hydroxyurea on hemodynamics of pregnant rabbits: a maternally mediated mechanism of embryotoxicity.
Hydroxyurea is a cytotoxic agent used in the management of chronic granulocytic leukemia. This compound is teratogenic and embryolethal in various animal species, and has been widely used in experimental studies aimed at understanding the possible mechanisms of drug-induced malformations. Previous studies from our laboratory have demonstrated that maternal subcutaneous injections of hydroxyurea produce immediate circulatory alterations in rabbit embryos similar to those observed subsequent to uterine artery occlusion. The present study was designed to investigate the possibility that the embryolethal and teratogenic properties of hydroxyurea might be due to alterations in maternal hemodynamics, i.e., constriction of the uterine vasculature, resulting in exposure of the embryo to uterine ischemia at critical stage of in utero development. This study demonstrates that hydroxyurea significantly alters blood pressure and heart rate and produces significant uterine vasoconstriction. The resulting reductions in uterine blood flow (77%) elicited by hydroxyurea may be associated with its immediate embryotoxicity.
D000014:Abnormalities, Drug-Induced / Q000209:etiology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006918:Hydroxyurea / Q000494:pharmacology*; D011247:Pregnancy; D011249:Pregnancy Complications, Cardiovascular / Q000503:physiopathology*; D011817:Rabbits; D012039:Regional Blood Flow; D014599:Uterus / Q000098:blood supply; D014655:Vascular Resistance / Q000187:drug effects
D006918:Hydroxyurea