Features of endothelial dysfunction and morphofunctional changes of the uteroplacental complex in experimentally induced pre-eclampsia.

Abstract

Pre-eclampsia is considered to be a severe complication of pregnancy. Theoretical investigation of its etiology and pathogenesis, development of strategies for its prevention and treatment are conditioned by the development of appropriate experimental models of this pathology. The study involved Wistar rat lines weighing 220-240g. Experimental pre-eclampsia was modeled by replacing drinking water consumed by pregnant female rats with 1.8% NaCl solution throughout gestation. Arterial pressure, protein concentration in urine and tissue hydration extent were measured on the 1st and 21st days of gestation. Uteroplacental blood flow, vasodilating and antithrombotic endothelial functions were also assessed. For pathomorphological and immunohistochemical investigation murine monoclonal antibodies against vascular endothelial growth factor (VEGF), polyclonal rabbit antibodies against inducible and endothelial NO-synthases were used. Replacing drinking water with 1.8% NaCl solution in female rats throughout gestation elevates arterial pressure, causes proteinuria and edema, impairs vasodilating and antithrombotic endothelial properties, and suppresses uteroplacental blood circulation. A morphological examination of the animals revealed the signs of focal duodenitis, spasms of myometrium arteries with no invasion of syncytiotrophoblast into its walls which also involved a raised VEGF and reduced eNOS expression in the endothelium of myometrial vessels, as well as cytoplasmic expression of iNOS in the cells of inflammatory infiltrate. These findings make it possible to conclude that replacing drinking water with 1.8% NaCl solution causes a number of changes typical of pre-eclampsia and, therefore, can be regarded as an experimental model of this pathologic condition.