PREGNANCY-INDUCED HYPERTENSION - A ROLE FOR PEROXIDATION IN MICROVILLUS PLASMA-MEMBRANES

It has been recently hypothesized that in PIH a placental oxidant-anti oxidant imbalance might cause the release of lipoperoxidation products into the circulation, with subsequent damage of endothelial cell memb ranes. In this hy pothesis the endothelial cell and further increase i n circulating lipoperoxide levels, which are by themselves able to ind uce smooth muscle constriction and increased presser responsiveness to angiotensin II. In order to investigate this issue, we studied the ba sal content of lipid peroxides in terms of malondialdehyde (MDA) in th e 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 compositi on of the membranes was also analyzed. Microvillus membrane lipoperoxi de 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 polyunsatur ated arachidonic acid. The increased susceptibility to oxidative stres s of SPMs from PIH women might be due either to reduced antioxidant sy stems or to an abnormality of the lipid composition of the membrane. T he present work also demonstrated in PIH a reduction in the SPM conten t of saturated fatty acids with an increase in polyunsaturated fatty a cids, which are the major substrate for peroxidation. On the other han d, the higher lipoperoxidation may be due to the observed increased su sceptibility to peroxidative stress, to a primary reduction in placent al perfusion with tissue hypoxia or to both factors, which can potenti ate each other.