Pregnancy induced hypertension: a role for peroxidation in microvillus plasma membranes

Abstract

It has been recently hypothesized that in PIH a placental oxidant-antioxidant imbalance might cause the release of lipoperoxidation products into the circulation, with subsequent damage of endothelial cell membranes. In this hypothesis the endothelial cell and further increase in circulating lipoperoxide levels, which are by themselves able to induce smooth muscle constriction and increased pressor responsiveness to angiotensin II. In order to investigate this issue, we studied the basal content of lipid peroxides in terms of malondialdehyde (MDA) in the syncytiotrophoblast plasma membranes (SPM) from PIH women. Moreover, we investigated the susceptibility to peroxidation of SPM using an in vitro oxidative stress as a tool to verify the predisposition to the in vivo development of peroxidation products. The fatty acid composition of the membranes was also analyzed. Microvillus membrane lipoperoxide concentrations were significantly increased in PIH women (62.8 +/- 7.6 ng MDA/mg prot) compared with healthy pregnant subjects (37.6 +/- 4.8 ng MDA/mg prot; p < 0.01). The formation of TBARS under the action of phenylhydrazine was significantly greater in PIH women (90.3 +/- 7.4 mmol MDA/mol cholesterol) than in normal pregnant subjects (68.6 +/- 6.4 mmol MDA/mol cholesterol; p < 0.01). In PIH microvillus membrane we also observed a significant increase of the content of polyunsaturated arachidonic acid. The increased susceptibility to oxidative stress of SPMs from PIH women might be due either to reduced antioxidant systems or to an abnormality of the lipid composition of the membrane.(ABSTRACT TRUNCATED AT 250 WORDS)

Hypertension in pregnancy

“…The role of placental fragments may also relate to local oxidative stress. There is evidence that villous membranes are oxidatively modified in PE 119 and fragments of these modified tissue could induce distant endothelial oxidative modification. The altered membrane fluidity of these membranes would favour their shedding, as would apoptosis known to be induced by oxidative stress.…”

Summary of the NHLBI Working Group on Research on Hypertension During Pregnancy

“…Reduced superoxide dismutase 70,72 Reduced glutathione peroxidase 73 Lipid markers Increased malondialdehyde 74 Increased lipid peroxides 73 Protein carbonyls 69 and neutrophils or monocytes activated directly in the intervillous space or by material (placental fragments or cytokines) from the hypoxic placenta. Furthermore, the identification of angiotensin antibodies with the capability to activate NADPH oxidase with subsequent free radical formation in women with preeclampsia suggests a very different origin for oxidative stress.…”

Iron Deficiency Anemia: A Public Health Problem of Global Proportions

“…Elevated CRH is a major risk factor for preterm labour, pregnancy-induced hypertension, eclampsia, premature rupture of the membranes, maternal infection (leading to yet more CRH synthesis), and increased fetal cortisol production (inhibiting longitudinal growth of the fetus) (Allen, 2001;Falkenberg et al, 1999;Lin et al, 1998;Linton et al, 1990, McLean et al, 1995. A second theory suggests that iron deficiency may increase oxidative damage to erythrocytes and the fetal-placental unit (Cester et al, 1994;Poranen et al, 1996).…”