Implantation, Pregnancy and Parturition
(T602) CHARACTERIZATION OF ENDOTHELIN RESPONSES IN ACUATE UTERINE ARTERIES OF THE PREGNANT RAT.
Guerin, Pascale1, 2, Sicotte, Benoit1, St-Louis, Jean1, 2, 1 Research Center, CHU Ste-Justine, Montreal, PQ, Canada2 Universite de Montreal, Montreal, PQ, Canada
ABSTRACT- During pregnancy, uterine circulation undergoes important structural and functional modifications to satisfy fetal developmental requirements. During gestation, arcuate uterine arteries double their diameter and increase their reactivity to vasoconstrictor agents. The effects of endothelin (ET), a powerful vasoconstrictor, have never been studied on these vessels. To perform pharmacological characterization of endothelin receptors (ETA, ETB) implicated in the contractile response to ET in the arcuate uterine artery and to determine the alterations induced by pregnancy. We have measured, using myographs for microvessels, contractile responses of arcuate arteries. The arteries were stretched to mimic a passive tension of 50 mm of Hg and were exposed to different ET analogs, with and without selective antagonists. Western blots were used to evaluate expression of ET receptors. Maximal responses to ET-1 and ET-3 were increased in arcuate arteries of pregnant compared to non pregnant rats. ET-1 was more powerful than ET-3 to contract arcuate uterine arteries of non pregnant rats but both agonists produced equivalent responses during pregnancy. Responses to sarafotoxin 6c (S6c), an ETB agonist, were only obtained in arteries of pregnant rats. BQ 123, an ETA antagonist, significantly inhibits ET-1 responses exclusively in arcuate arteries of non pregnant rats. BQ 788, an ETB antagonist, strongly shifted to the right S6c response-curve of pregnant rats arteries. Moreover, combination of both antagonists only partially inhibited ET-1 contraction in arteries of pregnant rats. Responses to ET-1 were importantly inhibited by ibuprofen, a cycloxygenase inhibitor. These results suggest that the contractile response to endothelin is mediated by the ETA receptor in arcuate uterine arteries of non pregnant rats, while the ETB receptors appear to be implicated during pregnancy. Moreover, ET-1 responses are partly mediated through endogenous liberation of cyclooxygenases products.
KEY WORDS: endothelin, receptor ETA and ETB, hypetension, pregnancy