1.
Novel ideas about salt, blood pressure, and pregnancy.
Rakova, N, Muller, DN, Staff, AC, Luft, FC, Dechend, R
Journal of reproductive immunology. 2014;:135-139
Abstract
The molecular mechanisms leading to preeclampsia are poorly understood. It has been related to certain immune mechanisms, as well as the pathological regulation of the renin-angiotensin system together with perturbed salt and plasma volume regulation. Finally, a non-specific, vascular, inflammatory response is generated, which leads to the clinical syndrome. Here, we present novel findings in salt (NaCl) metabolism implying that salt is not only important in blood pressure control and volume homeostasis, but also in immune regulation. Sodium and chloride can be stored without accumulation of water in the interstitium at hypertonic concentrations through interactions with proteoglycans. Macrophages in the interstitium act as osmosensors for salt, producing increased amounts of vascular endothelial factor C, which increases the density of the lymph-capillary network and the production of nitric oxide in vessels. An increased interstitial salt concentration activates the innate immune system, especially Th17 cells, and may be an important trigger for autoimmune diseases. The novel findings with the idea of sodium storage and local mechanisms of volume and immune regulation are appealing for preeclampsia and may unify the "immune" and "vascular" hypotheses of preeclampsia.
2.
A hypothesis for preeclampsia: adenosine and inducible nitric oxide synthase in human placental microvascular endothelium.
Escudero, C, Sobrevia, L
Placenta. 2008;(6):469-83
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.
3.
Maternal-fetal metabolism in normal pregnancy and preeclampsia.
von Versen-Hoeynck, FM, Powers, RW
Frontiers in bioscience : a journal and virtual library. 2007;:2457-70
Abstract
Adaptation to pregnancy in humans involves major anatomic, physiologic and metabolic changes in the mother in order to support and provide for the nutritional and metabolic needs of the growing conceptus. Metabolically, pregnancy is marked by several important and dynamic adjustments including increased insulin resistance, hyperlipidemia and changes in protein and amino acid metabolism. In general, these metabolic adaptations serve to increase nutrient availability for the benefit of the growing fetal-placental unit. Interestingly, the pregnancy complication preeclampsia is recognized to evidence biologic exaggerations of these normal metabolic adaptations of pregnancy. Specifically, preeclampsia is associated with increased insulin resistance, hypertriglyceridemia, high circulating free fatty acids, low high-density lipoprotein particles, and high maternal and fetal plasma amino acid concentrations. These metabolic alterations may contribute to the pathophysiology of the syndrome and may also influence fetal growth. The focus of this review will be to summarize the normal metabolic adaptations, transport and utilization of carbohydrates, lipids and amino acids that occur during pregnancy. Furthermore, we will review the differences in carbohydrate, lipid and amino acid metabolism in pregnancies complicated by preeclampsia in comparison to uncomplicated pregnancies.