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This Article Full Text Full Text (PDF) All Versions of this Article: 293/1/H520    most recent 01094.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by Tesse, A. Articles by Andriantsitohaina, R. Search for Related Content PubMed PubMed Citation Articles by Tesse, A. Articles by Andriantsitohaina, R.

Microparticles from preeclamptic women induce vascular hyporeactivity in vessels from pregnant mice through an overproduction of NO

¹UMR Centre National de la Recherche Scientifique 6214 Institut National de la Santé et de la Recherche Médicale 771, Faculté de Médecine, Angers; ²Institut Gilbert-Laustriat, UMR Centre National de la Recherche Scientifique 7175, Faculté de Pharmacie, Illkirch; and ³Service de Réanimation Médicale and ⁴Département de Gynécologie et d'Obstétrique, Hôpital de Hautepierre, Hôpitaux Universitaires de Strasbourg, Strasbourg, France

Submitted 5 October 2006 ; accepted in final form 15 March 2007

Preeclampsia is associated with an increase of circulating levels of microparticles (MPs), but their role in vascular dysfunction during the course of preeclampsia is not understood. Inasmuch as preeclampsia is a gestational disease, we tested the effect of MPs from preeclamptic women (PrMPs) and MPs from normal pregnant women (CMPs) on vessels from pregnant mice. We exposed aortic rings from pregnant mice to circulating levels of PrMPs or CMPs for 24 h and evaluated their response to serotonin (5-HT). PrMPs, but not CMPs, were able to induce hyporeactivity in response to 5-HT in aortas from pregnant mice. The nitric oxide (NO) synthase inhibitor N^G-nitro-L-arginine strongly enhanced the response to 5-HT in PrMP-treated vessels but had no significant effect on CMP-treated vessels. The 5-HT-induced contraction in PrMP-treated vessels was completely abolished by the selective cyclooxygenase-2 (COX-2) inhibitor NS-398 but was only reduced in CMP-treated vessels, suggesting an increased participation of COX-2 vasoconstrictor products in the effect of PrMPs. Consistent with this hypothesis, PrMPs enhanced levels of 8-isoprostane and PGE₂ in vessels, despite reduction of thromboxane B₂. These results strengthen the main concept that MPs in preeclampsia could act as vectors to stimulate intracellular cascades in vascular cells, leading to an enhanced NO production to counteract increased COX-2 vasoconstrictor metabolites by taking into account pregnancy.

pregnancy; nitric oxide; prostaglandin; preeclampsia