Preeclampsia Rats Research Articles

Bestatin results in pathophysiological changes similar to preeclampsia in rats via induction of placental apoptosis.

To establish a rat preeclampsia model with fetoplacental growth restriction caused by bestatin via induction of placental apoptosis. 200 mg/kg/day of bestatin or saline as a control were infused intraperitoneally into pregnant Wistar rats from 15 days' gestation. In the first experiment, maternal blood pressure and proteinuria were examined during the pre- and postpartum periods. In the second experiment, cesarean sections were performed at 20 days' gestation and the weights of pups and placentas, and levels of proteinuria and placental apoptosis were examined. Physiological decrease of blood pressure in late pregnancy was not detected in the bestatin group but proteinuria level at 20 days' gestation was elevated. The weights of pups and placentas in the bestatin group were significantly lower than those in the controls, bestatin strongly inducing apoptosis in the placenta. Bestatin may cause a preeclampsia-like condition through induction of placental apoptosis.

Acetylcholine-Induced Vasodilation in the Uterine Vascular Bed of Pregnant Rats with Adriamycin-Induced Nephrosis

Objective: This project was designed to study endothelium-dependent vasodilation in the uterine vascular bed during experimentally induced preeclampsia in rats. Methods: Uterine vascular beds were isolated from nonpregnant and pregnant rats with or without treatment with adriamycin (ADR) and perfused with physiological solution. Thereafter, vasodilator responses to acetylcholine were recorded. Records: Pregnant ADR-treated rats displayed symptoms of preeclampsia including hypertension and proteinuria. Blood pressure was 110.0 ± 4.7 mm Hg (n = 5) in control pregnant rats and 136.0 ± 5.3 mm Hg (n = 5) in ADR-treated pregnant rats, and urinary protein concentrations were 0.35 mg/ml (n = 5) and 13.2 ± 3.6 mg/ml (n = 9), respectively. Both blood pressure and proteinuria values were significantly (p < 0.05) different between controls and ADR-treated rats. However, acetylcholine-induced dose-dependent vasodilator responses in the vascular beds were not significantly different between the pregnant and nonpregnant rats. Although acetylcholine-induced vasodilation was significantly reduced by Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME) in both groups, the residual response to acetylcholine was not affected by indomethacin, suggesting that prostanoids were not involved in this response. The L-NAME-resistant component, endothelium-derived hyperpolarizing factor (EDHF), was greater in ADR-treated uterine beds than in those of the controls, indicating a significant contribution from EDHF in these vessels. In the presence of an elevated external potassium ion concentration, acetylcholine produced similar vasodilator responses, indicating that the release of nitric oxide was not impaired. Conclusion: These results indicate that endothelium-dependent vasodilation was not impaired in this model of preeclampsia.

The effect of indomethacin and prostacyclin agonists on blood pressure in a rat model of preeclampsia

Objective: This study was designed to determine the effects of cyclooxygenase inhibition and prostacyclin agonists on the hypertension induced by nitric oxide synthase blockade in a previously characterized rat model of preeclampsia. Study Design: A condition similar to preeclampsia was induced by infusing pregnant rats with the nitric oxide synthase inhibitor N G -nitro- L -arginine methyl ester through subcutaneously implanted osmotic minipumps. Blood pressure was measured with the tail cuff method. In the first experiment the rats received either vehicle alone (control group), N G -nitro- L -arginine methyl ester (50 mg/d), indomethacin (0.1 mg/d), or N G -nitro- L -arginine methyl ester plus indomethacin beginning on day 17 of pregnancy. In the second experiment the rats received vehicle alone (control group), N G -nitro- L -arginine methyl ester (50 mg/d), or N G -nitro- L -arginine methyl ester plus iloprost (31 μg/d). In a third experiment cicaprost (15 μg/d) was substituted for iloprost. Results: Except for an increase on the day after insertion of the pump indomethacin had no significant effect on the hypertension induced by N G -nitro- L -arginine methyl ester. Both prostacyclin agonists (iloprost and cicaprost), however, attenuated the rise in blood pressure usually seen after N G -nitro- L -arginine methyl ester administration. Conclusions: Nonselective inhibition of the cyclooxygenase enzymatic system does not influence the hypertension seen in the rat preeclampsia model induced by chronic nitric oxide deficiency. The hypertension in this model can be partially reversed with prostacyclin analogs. (Am J Obstet Gynecol 1999;180:1191-5.)

Lack of beneficial effects on the NO-donor, molsidomine, in the L-NAME-induced pre-eclamptic syndrome in pregnant rats.

1. In pregnant rats, chronic NO-synthase inhibition induces the development of a pre-eclamptic syndrome, characterized by an increase in maternal blood pressure, a loss of vascular refractoriness to pressor stimuli, a reduction in litter size and a decrease in pups (and maternal) weight. We investigated whether a NO-donor, molsidomine, administered during NO synthase inhibition, could restore a normal pregnancy. 2. Pregnant rats were given daily, starting from day 14 of gestation, saline (controls), or L-NAME (50 mg kg-1 d-1), or molsidomine (15 or 30 mg kg-1 d-1), or the L-NAME + molsidomine combinations. Maternal blood pressure and body weight, litter size, pups weight and vascular reactivity to pressor stimuli (angiotensin II, noradrenaline, electrical stimulation of the spinal cord) were investigated. 3. L-NAME alone, as compared to controls, increased maternal blood pressure, reduced litter size (-59%), increased foetal reabsorptions (+ 625%) and decreased foetal weight (-10%). Vascular reactivity to pressor stimuli was enhanced. 4. Molsidomine alone, as compared to controls, dose-dependently decreased maternal blood pressure but had no effect vascular reactivity and, whatever the dose, on foetal outcome. 5. The L-NAME-molsidomine combinations dose (of molsidomine)-dependently limited the rise in maternal blood pressure induced by L-NAME alone but unexpectedly, dose-dependently and significantly worsened pregnancy evolution, e.g., at 30 mg kg-1 d-1: litter size (-80%), foetal reabsorptions (+ 1025%), foetal weight (-24%). Vascular reactivity to pressor stimuli was paradoxically further enhanced. 6. Thus, in a chronic NO deprivation-induced model of pre-eclampsia in rats, molsidomine, possibly because of its hypotensive action, worsens the foetal outcome, which questions the usefulness of NO-donors in pre-eclamptic women.

Calcitonin gene-related peptide reverses the hypertension and significantly decreases the fetal mortality in pre-eclampsia rats induced by NG-nitro-L-arginine methyl ester

We recently established that the chronic inhibition of nitric oxide production with N(G)-nitro-L-arginine methyl ester (L-NAME) increases blood pressure and fetal mortality in pregnant rats. Using this animal model, we have investigated whether calcitonin gene-related peptide (CGRP) can reverse the pre-eclampsia-like conditions produced by L-NAME. CGRP and L-NAME were chronically infused s.c. into pregnant rats separately or together starting on day 17 of gestation; a control group was given saline infusions. Systolic blood pressure was measured on gestational days 17, 18, 19 and 22 and post-partum days 1 and 2. The weight and mortality of the pups were recorded immediately after spontaneous delivery. Animals treated with L-NAME exhibited significant elevations of blood pressure on days 18, 19 and 22 of gestation and during post-partum, increased pup mortality (18.4 versus 0.0%) and decreased pup weights (5.14 +/- 0.07 versus 6.20 +/- 0.06 g). The co-administration of L-NAME and CGRP prevented the gestational (not the post-partum) L-NAME hypertension and decreased pup mortality to 6.4% but did not reverse the decreased fetal weight (5.31 +/- 0.06 g). Our data indicate the CGRP (i) participates in regulation of the vascular adaptations that occur during normal pregnancy, (ii) has beneficial effects on the hypertension and increased mortality of experimental preeclampsia, and (iii) may exert differential effects on the systemic (i.e. maternal) and fetal components of utero-placental circulation. These findings may have important clinical implications.