title: A hypothesis for preeclampsia: adenosine and inducible nitric oxide synthase in human placental microvascular endothelium.
abstract: Preeclampsia is a human syndrome characterized by elevated maternal blood pressure and proteinuria. It is the main cause of maternal morbidity and mortality, and fetal metabolic disturbances in developed and developing countries. Fetal complications in preeclampsia have been related with lower placental blood flow. The placenta lacks of innervation, thus vascular tone regulation depends on endothelial release of vasoactive molecules such as adenosine and nitric oxide (NO). Information about NO synthesis and its action in the feto-placental vasculature in preeclamptic pregnancies is controversial mainly due to the use of different methodological approaches, severity of the disease and cell type that had been analyzed. A high plasma level of adenosine has been reported in umbilical vein from preeclampsia compared with normal pregnancies. Since this nucleoside is mainly involved in the regulation of vascular tone and angiogenesis, perhaps through the modulation of potassium channels, it is suggested that it would be involved in the maintenance of normal feto-placental function. In this review we hypothesize a potential adenosine-mediated, NO-dependent mechanism accounting for the feto-placental reduced blood flow exhibited in preeclampsia. We summarize the potential mechanisms involved in the modulation of inducible NO synthase expression and activity in preeclampsia, emphasizing metabolic alterations in the placenta microvascular endothelial function. The involvement of adenosine, nucleoside membrane transporters and adenosine receptors, nuclear factor kappa B (NF-kappaB), potassium channels and angiogenesis, are also discussed regarding abnormal endothelial function in preeclampsia.
authors: Cellular and Molecular Physiology Laboratory, Department of Obstetrics and Gynaecology, Medical Research Centre (CIM), School of Medicine, Faculty of Medicine, Pontificia Universidad Católica de Chile, P.O. Box 114-D, Santiago, Chile.
authors: C
authors: C
authors: Escudero
authors: L
authors: L
authors: Sobrevia
mesh_terms: D000241:Adenosine / Q000378:metabolism*; D001120:Arginine / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism*; D005260:Female; D006801:Humans; D008954:Models, Biological; D016328:NF-kappa B / Q000502:physiology; D018919:Neovascularization, Physiologic / Q000502:physiology; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D010920:Placenta / Q000098:blood supply* / Q000378:metabolism; D011225:Pre-Eclampsia / Q000378:metabolism*; D011247:Pregnancy; D015398:Signal Transduction / Q000502:physiology
chemical_list: D016328:NF-kappa B; D001120:Arginine; D052247:Nitric Oxide Synthase Type II; D000241:Adenosine