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

Abstract

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 PGE(2) in vessels, despite reduction of thromboxane B(2). 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.