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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Effect of GABA derivatives on the rate of thrombus formation, platelet aggregation, and plasma coagulation capacity in rats with experimental gestosis.

Experimental gestosis induced by replacement of drinking water with 1.8% NaCl promoted hypercoagulation, increased the rate and degree of platelet aggregation, and reduced clotting time in pregnant females. GABA derivatives, compounds RGPU-151, RGPU-152, and phenibut normalized parameters of hemostasis and platelet aggregation and the rate of thrombus formation in the animals. The efficiency of the test substances did not significantly differ from that of the reference drug sulodexide.

GABA derivatives citrocard and salifen reduce the intensity of experimental gestosis.

Substitution of drinking water with 1.8 % NaCl solution in pregnant female rats from day 1 of gestation until parturitions was followed by the development of experimental gestosis. Gestosis manifested in an increase in BP by 18.2 %, protein concentration in the urine by 6.2 times, and edema severity in muscles, brain, and omentum in comparison with the initial level. The concentration of homocysteine in blood plasma of rats with complicated pregnancy 4.4-fold surpassed that in pregnant rats without gestosis, which can probably in a cause for gestosis development. GABA derivatives citrocard (50 mg/kg) and salifen (15 mg/kg), and the reference substance sulodexide (30 U/kg) reduced the severity of gestosis manifestations, which was seen from the absence of BP rise, decrease in urinary protein concentration by 1.9, 2.0, and 1.3 times and blood level of homocysteine by 1.7, 1.5, and 2.6 times, respectively, and a decrease in edema degree in comparison with female rats with experimental gestosis receiving physiological saline.

[Effect of GABA derivative--RSMU-151 on the development of oxidative stress in rats with experimental gestosis].

Experimental gestosis induced in rats by drinking 1.8% sodium chloride solution instead of water during the entire period of pregnancy leads to activation of lipid peroxidation (LPO) process, as manifested by increased concentration of diene conjugates and malonic dialdehyde, decreased concentration of antioxidant enzymes (superoxide dismutase and glutathione peroxidase) in homogenates of rat brain, liver, uterus, and placenta. The GABA derivatives--RSMU-151 limits the damaging effect of gestosis, which is manifested by a decrease in the concentration of LPO products and by activation of the antioxidant system enzymes in all organs studied.