In Vivo Constriction of the Ductus Arteriosus by Nonsteroidal Antiinflammatory Drugs in Near-Term and Preterm Fetal Rats

Momma, Kazuo; Takao, Atsuyoshi

doi:10.1203/00006450-198711000-00018

Cited by 57 publications

(40 citation statements)

References 21 publications

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“…Previous studies in rats and humans have shown that the preterm fetal DA is less responsive to indomethacin-induced constriction, in contrast to the DA of full-term fetuses (19,20). In the current studies, we examined the effect of gestational age on indomethacin-induced fetal DA constriction in mice.…”

Section: Discussionmentioning

confidence: 99%

Attenuated Cyclooxygenase-2 Expression Contributes to Patent Ductus Arteriosus in Preterm Mice

2006

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Patent ductus arteriosus (DA) is the second most common congenital heart defect, the incidence of which is increased in premature infants, although mechanisms responsible are not clear. Our previous studies with genetic or pharmacological inactivation of cyclooxygenase-2 (COX-2) in mice, emphasized the importance of this enzyme in normal DA closure. The current study was designed to determine whether reduced COX-2 expression contributes to patent DA in preterm mice. Real-time PCR analysis indicated that COX-2 expression in the fetal mouse DA significantly increased with advancing gestational age. Furthermore, we observed a significant induction in COX-2 expression in the DA at 3 h after birth at full-term gestation. In contrast, COX-2 expression was significantly attenuated in the DA of preterm neonatal mice. DA closure was incomplete in preterm mice at 3 h postpartum, a time-point when the DA of full-term neonates was completely remodeled. Additionally, COX-2 expression was significantly attenuated in the DA of mice deficient in the prostanoid receptor EP4, which also show a patent DA phenotype, suggesting the importance of this receptor for the induction of COX-2 required for DA closure. Overall, these studies suggest that attenuated expression of COX-2 may contribute to increased patent DA at preterm gestation. (Pediatr Res 60: 669-674, 2006)

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Section: Discussionmentioning

confidence: 99%

Attenuated Cyclooxygenase-2 Expression Contributes to Patent Ductus Arteriosus in Preterm Mice

2006

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“…A dose of 3 mg/kg has been chosen as a dose which blocks whole body synthesis of prostaglandins (32). Because indomethacin crosses the placenta (4,33), and our fetuses would continue to have a placental circulation throughout the experiment, we treated both the ewe and fetus with 3 mg/kg of indomethacin to prevent losses across the placenta. Tyler et al (30), LeMer et al (4), and Redding et al (3 1) each used intervals of 30-45 min after administration to measure the effects of prostaglandin synthesis blockade.…”

Section: Resultsmentioning

confidence: 99%

Indomethacin Does Not Diminish the Pulmonary Vascular Response of the Fetus to Increased Oxygen Tension

1988

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ABSTRACT. This study was performed to determineOxygen is one of the major stimuli decreasing pulmonary whether prostaglandins play a role in the increase in pul-vascular resistance at birth (1,(13)(14)(15). Assali et al., (16) and monary blood flow in the fetal lamb caused by an increase Heymann et al., (17) isolated the effect of a rise in oxygen tension in oxygen tension similar to that occurring at birth. To from the effect of ventilation of the lungs with a gas in acutely increase fetal oxygen tension without ventilating the lungs, instrumented fetal lambs by placing pregnant ewes in a hypernine pregnant ewes with chronically instrumented fetuses baric chamber at several atmospheres of pressure. Morin et al.were exposed to 100% oxygen at 3 atmospheres absolute (18) adapted this technique to study chronically instrumented pressure for 20 min in a hyperbaric chamber. This expo-fetal lambs and found that the entire increase in pulmonary sure increased pulmonary arterial oxygen tension in the blood flow that normally occurs at birth could be produced by nine fetuses from 20 f 1 to 54 f 9 torr. It increased an increase in oxygen tension alone. pulmonary blood flow from fetal to newborn values, 31 fThe current study was performed to determine whether the 3 to 295 2 20 ml/kg/min. It did not change pulmonary response of the fetal pulmonary circulation to oxygen is mediated arterial pressure, 52 f 2 torr during normoxia and 50 f 2 by prostaglandins. We measured the ability of prostaglandin torr during hyperoxia. Treating five of these fetuses with synthesis blockade by indomethacin to diminish the increase in 3.2 f 0.4 mg/kg of indomethacin during hyperbaric oxy-fetal pulmonary blood flow caused by an increase in oxygen genation did not alter these effects (Po2 = 51 f 8 torr, tension. pulmonary blood flow = 283 f 13 ml/kg/min, and pulmonary arterial pressure = 48 f 2 torr). We conclude that gestation were prepared for study. A catheter was passed from the maternal jugular vein into the right atrium for sampling of Abbreviations blood and for induction of anesthesia with 700 mg of sodium thiamylal. Surgery was then performed with the pregnant ewe PGD2, prostaglandin D2 under halothane anesthesia. The uterus was exposed through an PGE2, prostaglandin Ez abdominal incision, and the fetal head and neck were delivered 6-keto-PGE2, prostaglandin E2 through a uterine incision. An incision was made in the fetal ATA, atmosphere absolute pressure neck, and catheters were inserted into the carotid artery for measurement of systemic pressure and via the jugular vein into the superior vena cava for injection of radioactive microspheres. A left thoracotomy was performed, and a catheter was inserted into the main pulmonary artery, proximal to the branching of At birth there is a dramatic decrease in pulmonary vascular the right and left pulmonary arteries and the ductus arteriosus, resistance and increase in pulmonary blood flow (1, 2). The for measurement of pressure; sampling of blood gases and withincrease in pulmonary blood f...

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“…It is well accepted that the constrictive response of the DA to indomethacin is an appropriate index of the DA differentiation [8,11,19,26]. We showed previously that the effect of indomethacin on the DA constriction was observed on days 19 2 /3 and later of gestation, and that the constrictive effect increased toward term [1].…”

Section: Discussionmentioning

confidence: 99%

Smooth Muscle Cell Proliferation in the Ductus Arteriosus and the Descending Aorta, and Effects of Enalapril on SMC Proliferation in Perinatal Rats.

Takizawa

Kawahata

Ikeda

et al. 1999

The Journal of Veterinary Medical Science

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ABSTRACT. This study was carried out to determine the proliferation profile of the smooth muscle cells (SMC) in the media of the ductus arteriosus (DA) and the descending aorta (Ao), and to examine the effects of the angiotensin-converting enzyme inhibitor enalapril on the proliferation of these cells in perinatal rats. The proliferating cell nuclear antigen (PCNA) index of the DA peaked in 19-day-old fetuses at 75%, and the index significantly declined in 20-day-old fetuses. The PCNA index of the Ao showed a similar profile until pups reached 1 day of age; however, the index of the Ao then increased in 3-day-old pups. The PCNA indices of the DA and Ao decreased significantly after maternal oral treatment with enalapril (10 mg/kg for 7 days), with a more marked decline in the DA than in the Ao. The PCNA indices of these vessels in 20-day-old fetuses were not altered by maternal treatment with enalapril. These results indicate that the SMC proliferation rate in the DA was similar to that in the Ao until pups reached the age of 1 day, and that the inhibitory effect of enalapril on the SMC proliferation was age-dependent and more prominent in the DA than in the Ao.-KEY WORDS: ductus arteriosus, enalapril, PCNA, proliferation, SMC.J. Vet. Med. Sci. 61(11): 1215-1218, 1999 investigated the PCNA labeling index to monitor the proliferating activity of the SMC, and we compared the effects of enalapril on SMC proliferation in the DA and the descending aorta (Ao). MATERIALS AND METHODSFemale Crj: Wistar rats, 10-12 weeks old at the time of mating, were used. They were maintained with commercial rat chow (CE-2, Clea Japan, Tokyo) and tap water ad libitum, and kept in a room at a temperature of 22 ± 3°C with a relative humidity of 55 ± 10%. Three females were placed with a male overnight, and were examined the next morning for the presence of sperm in a vaginal smear. The day when sperm was found was designated as day 0 of gestation, and the females were caged individually thereafter.To examine the age-related changes of the PCNA labeling indices of the DA and the Ao, fetuses were quickly removed from the uteri of mother rats from day 18 to day 21 of gestation, and 1 or 3 day-old newborn pups were obtained from witnessed deliveries. To examine the effect of enalapril on the PCNA labeling indices of these vessels, fetuses were obtained on day 19 or 20 of gestation from pregnant rats and were transplacentally administered enalapril (10 mg/kg) from day 12 or 13 for 7 consecutive days.Fetuses and newborn pups were decapitated, and then the thoracic cavity was opened and immersed in fresh fixative fluid. Fixation was performed in 100% ethanol for 24 hr, and the fixed materials were then freed of alcohol by treatment with xylene, embedded in Paraplast (Sherwood Closure of the ductus arteriosus (DA) is one of the most critical events for adaptation of mammals to extrauterine life. The ductal closure after birth occurs in two stages, i.e., initial closure and anatomical closure. Initial closure is brought about by contraction of th...

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In Vivo Constriction of the Ductus Arteriosus by Nonsteroidal Antiinflammatory Drugs in Near-Term and Preterm Fetal Rats

Cited by 57 publications

References 21 publications

Attenuated Cyclooxygenase-2 Expression Contributes to Patent Ductus Arteriosus in Preterm Mice

Attenuated Cyclooxygenase-2 Expression Contributes to Patent Ductus Arteriosus in Preterm Mice

Indomethacin Does Not Diminish the Pulmonary Vascular Response of the Fetus to Increased Oxygen Tension

Smooth Muscle Cell Proliferation in the Ductus Arteriosus and the Descending Aorta, and Effects of Enalapril on SMC Proliferation in Perinatal Rats.

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