dinoprost and Hyperoxia

Both hypoxia and hyperoxia have major effects on cardiovascular function. However, both states affect ventilation and many previous studies have not controlled CO(2) tension. We investigated whether hemodynamic effects previously attributed to modified O(2) tension were still apparent under isocapnic conditions. In eight healthy men, we studied blood pressure (BP), heart rate (HR), cardiac index (CI), systemic vascular resistance index (SVRI) and arterial stiffness (augmentation index, AI) during 1 h of hyperoxia (mean end-tidal O(2) 79.6 +/- 2.0%) or hypoxia (pulse oximeter oxygen saturation 82.6 +/- 0.3%). Hyperoxia increased SVRI (18.9 +/- 1.9%; P < 0.001) and reduced HR (-10.3 +/- 1.0%; P < 0.001), CI (-10.3 +/- 1.7%; P < 0.001), and stroke index (SI) (-7.3 +/- 1.3%; P < 0.001) but had no effect on AI, whereas hypoxia reduced SVRI (-15.2 +/- 1.2%; P < 0.001) and AI (-10.7 +/- 1.1%; P < 0.001) and increased HR (18.2 +/- 1.2%; P < 0.001), CI (20.2 +/- 1.8%; P < 0.001), and pulse pressure (13.2 +/- 2.3%; P = 0.02). The effects of hyperoxia on CI and SVRI, but not the other hemodynamic effects, persisted for up to 1 h after restoration of air breathing. Although increased oxidative stress has been proposed as a cause of the cardiovascular response to altered oxygenation, we found no significant changes in venous antioxidant or 8-iso-prostaglandin F(2alpha) levels. We conclude that both hyperoxia and hypoxia, when present during isocapnia, cause similar changes in cardiovascular function to those described with poikilocapnic conditions.

Topics: Adaptation, Physiological; Adult; Antioxidants; Blood Flow Velocity; Blood Pressure; Carbon Dioxide; Cardiac Output; Cross-Over Studies; Dinoprost; Female; Heart; Heart Rate; Humans; Hyperoxia; Hypoxia; Male; Middle Aged; Oxidative Stress; Oxygen; Single-Blind Method; Time Factors; Vascular Resistance

Infants with lung disease may be exposed to high O

Topics: Animals; Animals, Newborn; Antioxidants; Cell Hypoxia; Dinoprost; Hyperoxia; Hypoxia; Mitochondria; Myocytes, Smooth Muscle; NADPH Oxidases; Oxidative Stress; Pulmonary Artery; Superoxide Dismutase; Swine

Central Nervous System Oxygen Toxicity (CNS-OT) is one of the most harmful effects of Enriched Air Nitrox (EAN) diving. Protective factors of the Ketogenic Diet (KD) are antioxidant activity, the prevention of mitochondrial damage and anti-inflammatory mechanisms. We aimed to investigate if a short-term KD may reduce oxidative stress and inflammation during an hyperoxic dive. Samples from six overweight divers (mean ± SD, age: 55.2 ± 4.96 years; BMI: 26.7 ± 0.86 kg/m

Topics: Adult; Air; Decompression; Decompression Sickness; Deoxyguanosine; Diet, Ketogenic; Dinoprost; Diving; Exercise; Humans; Hyperoxia; Interleukin-1beta; Interleukin-6; Male; Middle Aged; Nitrogen; Overweight; Oxidative Stress; Oxygen; Pilot Projects; Prospective Studies; Tumor Necrosis Factor-alpha

Hyperoxia contributes to acute lung injury in diseases such as acute respiratory distress syndrome. Cytochrome P450 (CYP) 1A enzymes have been implicated in hyperoxic lung injury, but the mechanistic role of CYP1A2 in pulmonary injury is not known. We hypothesized that mice lacking the gene Cyp1a2 (which is predominantly expressed in the liver) will be more sensitive to lung injury and inflammation mediated by hyperoxia and that CYP1A2 will play a protective role by attenuating lipid peroxidation and oxidative stress in the lung. Eight- to ten-week-old WT (C57BL/6) or Cyp1a2(-/-) mice were exposed to hyperoxia (>95% O2) or maintained in room air for 24-72 h. Lung injury was assessed by determining the ratio of lung weight/body weight (LW/BW) and by histology. Extent of inflammation was determined by measuring the number of neutrophils in the lung as well as cytokine expression. The Cyp1a2(-/-) mice under hyperoxic conditions showed increased LW/BW ratios, lung injury, neutrophil infiltration, and IL-6 and TNF-α levels and augmented lipid peroxidation, as evidenced by increased formation of malondialdehyde- and 4-hydroxynonenal-protein adducts and pulmonary isofurans compared to WT mice. In vitro experiments showed that the F2-isoprostane PGF2-α is metabolized by CYP1A2 to a dinor metabolite, providing evidence for a catalytic role for CYP1A2 in the metabolism of F2-isoprostanes. In summary, our results support the hypothesis that hepatic CYP1A2 plays a critical role in the attenuation of hyperoxic lung injury by decreasing lipid peroxidation and oxidative stress in vivo.

Topics: Aldehydes; Animals; Cytochrome P-450 CYP1A2; Dinoprost; F2-Isoprostanes; Hyperoxia; Interleukin-6; Leukocyte Count; Lipid Peroxidation; Liver; Lung Injury; Malondialdehyde; Mice; Mice, Inbred C57BL; Mice, Knockout; Neutrophil Infiltration; Neutrophils; Oxidative Stress; Tumor Necrosis Factor-alpha

Sex-specific differences in pulmonary morbidity in humans are well documented. Hyperoxia contributes to lung injury in experimental animals and humans. The mechanisms responsible for sex differences in the susceptibility towards hyperoxic lung injury remain largely unknown. In this investigation, we tested the hypothesis that mice will display sex-specific differences in hyperoxic lung injury. Eight week-old male and female mice (C57BL/6J) were exposed to 72 h of hyperoxia (FiO2>0.95). After exposure to hyperoxia, lung injury, levels of 8-iso-prostaglandin F2 alpha (8-iso-PGF 2α) (LC-MS/MS), apoptosis (TUNEL) and inflammatory markers (suspension bead array) were determined. Cytochrome P450 (CYP)1A expression in the lung was assessed using immunohistochemistry and western blotting. After exposure to hyperoxia, males showed greater lung injury, neutrophil infiltration and apoptosis, compared to air-breathing controls than females. Pulmonary 8-iso-PGF 2α levels were higher in males than females after hyperoxia exposure. Sexually dimorphic increases in levels of IL-6 (F>M) and VEGF (M>F) in the lungs were also observed. CYP1A1 expression in the lung was higher in female mice compared to males under hyperoxic conditions. Overall, our results support the hypothesis that male mice are more susceptible than females to hyperoxic lung injury and that differences in inflammatory and oxidative stress markers contribute to these sex-specific dimorphic effects. In conclusion, this paper describes the establishment of an animal model that shows sex differences in hyperoxic lung injury in a temporal manner and thus has important implications for lung diseases mediated by hyperoxia in humans.

Topics: Acute Lung Injury; Animals; Apoptosis; Biomarkers; Blotting, Western; Dinoprost; Female; Humans; Hyperoxia; Immunohistochemistry; In Situ Nick-End Labeling; Lung Injury; Male; Mice; Mice, Inbred C57BL; Neutrophil Infiltration; Oxidative Stress; Sex Characteristics

Sepsis is the most common cause of death in intensive care units. Some studies have found that hyperoxia may be beneficial to sepsis. However, the clinical use of hyperoxia is hindered by concerns that it could exacerbate organ injury by increasing free radical formation. Recently, it has been suggested that molecular hydrogen (H2) at low concentration can exert a therapeutic antioxidant activity and effectively protect against sepsis by reducing oxidative stress. Therefore, we hypothesized that combination therapy with H2 and hyperoxia might afford more potent therapeutic strategies for sepsis. In the present study, we found that inhalation of H2 (2%) or hyperoxia (98%) alone improved the 14-day survival rate of septic mice with moderate cecal ligation and puncture (CLP) from 40% to 80% or 70%, respectively. However, combination therapy with H2 and hyperoxia could increase the 14-day survival rate of moderate CLP mice to 100% and improve the 7-day survival rate of severe CLP mice from 0% to 70%. Moreover, moderate CLP mice showed significant organ damage characterized by the increases in lung myeloperoxidase activity, lung wet-to-dry weight ratio, protein concentration in bronchoalveolar lavage, serum biochemical parameters (alanine aminotransferase, aspartate aminotransferase, creatinine, and blood urea nitrogen), and organ histopathological scores (lung, liver, and kidney), as well as the decrease in PaO2/FIO2 ratio at 24 h, which was attenuated by either H2 or hyperoxia alone. However, combination therapy with H2 and hyperoxia had a more beneficial effect against lung, liver, and kidney damage of moderate or severe CLP mice. Furthermore, we found that the beneficial effect of this combination therapy was associated with the decreased levels of oxidative product (8-iso-prostaglandin F2α), increased activities of antioxidant enzymes (superoxide dismutase and catalase) and anti-inflammatory cytokine (interleukin 10), and reduced levels of proinflammatory cytokines (high-mobility group box 1 and tumor necrosis factor α) in serum and tissues. Therefore, combination therapy with H2 and hyperoxia provides enhanced therapeutic efficacy via both antioxidant and anti-inflammatory mechanisms and might be potentially a clinically feasible approach for sepsis.

Topics: Alanine Transaminase; Animals; Catalase; Coinfection; Cytokines; Dinoprost; Disease Models, Animal; Glutamyl Aminopeptidase; Hydrogen; Hyperoxia; Inflammation Mediators; Kidney; Liver; Lung; Male; Mice; Peroxidase; Sepsis; Superoxide Dismutase

We investigated the influence of oxygenation of in vitro lung preparation on the pulmonary vascular reactivity. Small pulmonary vessels isolated from adult male Wistar rats exposed for 4 days to hypoxia (F(iO2) = 0.1, group CH) were compared with those of normoxic controls (group N). The bath in the chamber of small vessel myograph was saturated with gas mixture containing either 21% or 95% of O(2) with 5% CO(2) and we measured the reactions of vessels to acute hypoxic challenge with 0% O(2) or to PGF(2alpha). We did not observe any difference of the contractile responses between both groups when the normoxic conditions were set in the bath. When the bath oxygenation was increased to 95% O(2), the contractions induced by hypoxic challenge and PGF(2alpha) decreased in chronically hypoxic rats and did not change in normoxic controls. We hypothesize that reduced reactivity of vessels from hypoxic rats in hyperoxia results from the effect of chronic hypoxia on Ca(2+) signaling in the vascular smooth muscle, which is modulated by increased free radical production during the exposure to chronic hypoxia and further hyperoxia.

Topics: Animals; Calcium Signaling; Chronic Disease; Dinoprost; Hyperoxia; Hypoxia; In Vitro Techniques; Male; Myography; Pulmonary Artery; Rats; Rats, Wistar; Vasoconstriction; Vasoconstrictor Agents

To investigate the role of oxidative stress in the pathogenesis of retinal injury induced by hyperoxia.. Sixty immature Sprague-Dawley (SD) rats born at a gestational age of 21 days, were randomly exposed to room air (air group, n=30) or 95% oxygen (hyperoxia group, n=30) immediately after birth. Plasma 8-iso-prostaglandin F2alpha (8-iso-PGF2alpha) levels were determined by ELISA. The ultrastructures of the retina were observed under a transmission electron microscope.. The plasma 8-iso-PGF2alpha contents of the air group were 19.09 +/-5.57, 18.24+/-5.91 and 17.00 +/- 5.58 pg/mL on the 3rd, 7th and 14th days after birth, respectively (F=1.024, P> 0.05). The plasma 8-iso-PGF2 contents in the hyperoxia group on the 3rd (28.33 +/- 5.59 pg/mL), the 7th day (51.20 +/- 15.01 pg/mL) and 14th day (84.54 +/- 14.85 pg/mL) after birth were significantly higher than those of the air group (t=2.863, P< 0.05; t=5.073, P< 0.01; t=11.006, P< 0.01). Moreover, the plasma 8-iso-PGF2 contents in the hyperoxia group increased with the prolonged hyperoxia exposure (F=150.7, P < 0.01). The ultrastructures of retina in the air group were normal. Hyperoxia exposure resulted in abnormalities of the ultrastructures of retina, manifesting as the membrane discs rarefied, twisted and disrupted and mitochondrial swelling.. Oxidative stress can results in retinal injury in immature rats. An increased plasma level of 8-iso-PGF2alpha is related to the injury degree of retina.

Topics: Animals; Dinoprost; Humans; Hyperoxia; Infant, Newborn; Lipid Peroxidation; Oxidative Stress; Rats; Rats, Sprague-Dawley; Retina; Retinopathy of Prematurity

Inflammation contributes greatly to the pathogenesis of bronchopulmonary dysplasia. In previous studies, we showed that blocking neutrophil influx by treatment with SB265610, a selective CXCR2 antagonist, could partly reduce superoxide accumulation and preserve alveolar development in 60% O(2)-exposed newborn rats. The purpose of this study was to further investigate the role of neutrophils in the formation of reactive oxygen and nitrogen species mediating hyperoxia-impaired lung development. We found that hydroxyl radical formation and lipid peroxidation in rat lungs were significantly increased during 60% O(2) exposure. These increases were attenuated by the administration of SB265610. In addition, SB265610 largely inhibited protein nitration induced by hyperoxia. SB265610 partly prevented the hyperoxia-enhanced bronchoalveolar lavage (BAL) protein content in 60% O(2)-exposed animals. Our results demonstrate that neutrophils have a pivotal role in hydroxyl radical formation, lipid peroxidation and protein nitration. Taken together with our previous studies, the present findings show that blocking neutrophil influx protects alveolar development and improves lung function in part by preventing reactive oxygen/nitrogen species accumulation.

Topics: Animals; Animals, Newborn; Dinoprost; Hydroxyl Radical; Hyperoxia; Lung; Neutrophils; Oxygen; Rats; Reactive Nitrogen Species; Reactive Oxygen Species; Receptors, Interleukin-8B; Tyrosine

Hyperoxic pretreatment (>95% O(2)) can evoke myocardial adaptation to ischemia, a method which is potentially clinically usable. We wanted to investigate the role of tumor necrosis factor alpha (TNFalpha) and its p55 receptor (receptor I) in signaling of hyperoxic adaptation to ischemia. Mice deficient for TNFalpha (TNFalpha -/-) or the TNF receptor I (TNFRI -/-) gene and their wild types were subjected to 60 minutes of hyperoxia or sham treatment. Their lungs were then collected for immunoblotting, their hearts isolated and subjected to global ischemia and reperfusion in a Langendorff system, and aortic rings mounted in organ baths for reactivity studies. Hyperoxia increased expression of TNFalpha and TNFalpha converting enzyme in pulmonary proteins from wild type mice, in which hyperoxia increased myocardial tolerance to ischemia. Post-ischemic heart function was improved and infarct size reduced in wild type mice, but not in TNFalpha -/- or TNFRI -/-. The contractile response to TNFalpha on aortic rings was attenuated by hyperoxic pretreatment and by TNFRI -/-. Thus we conclude that TNFalpha, acting through TNFRI, appears important for the protective effects of hyperoxia.

Topics: Acetylcholine; ADAM Proteins; ADAM17 Protein; Animals; Aorta; Dinoprost; Enzyme-Linked Immunosorbent Assay; Hyperoxia; Ischemic Preconditioning, Myocardial; Mice; Mice, Inbred C57BL; Mice, Knockout; Myocardial Infarction; Myocardial Ischemia; Nitroprusside; Phenylephrine; Receptors, Tumor Necrosis Factor, Type I; Tumor Necrosis Factor-alpha; Vasoconstrictor Agents; Vasodilator Agents; Ventricular Pressure

Chronic oxygen exposure in the newborn rat results in lung isoprostane formation, which may contribute to the pulmonary hypertension evident in this animal model. The purpose of this study was to investigate the pulmonary arterial smooth muscle responses to 8-iso-prostaglandin F(2alpha) (8-iso-PGF(2a)) in newborn rats exposed to 60% O2 for 14 days. Because, in the adult rat, 8-iso-PGF(2alpha) may have a relaxant effect, mediated by nitric oxide (NO), we also sought to evaluate the pulmonary arterial NO synthase (NOS) protein content and NO release in the newborn exposed to chronic hyperoxia. Compared with air-exposed control animals, 8-iso-PGF(2a) induced a significantly greater force (P < 0.01) and reduced (P < 0.01) relaxation of precontracted pulmonary arteries in the 60% O2-treated animals. These changes were reproduced in control pulmonary arteries by NOS blockade by using NG-nitro-L-arginine methyl ester. Pulmonary arterial endothelial NOS was unaltered, but the inducible NOS protein content was significantly decreased (P < 0.01) in the experimental group. Pulmonary (P < 0.05) and aortic (P < 0.01) tissue ex vivo NO accumulation was significantly reduced in the 60% O2-treated animals. We speculate that impaired pulmonary vascular tissue NO metabolism after chronic O2 exposure potentiates 8-iso-PGF(2alpha)-induced vasoconstriction in the newborn rat, thus contributing to pulmonary hypertension.

Topics: Animals; Animals, Newborn; Chronic Disease; Dinoprost; Female; Hyperoxia; Hypertension, Pulmonary; Isoprostanes; Muscle, Smooth, Vascular; Nitric Oxide; Nitric Oxide Synthase; Oxygen; Pregnancy; Pulmonary Artery; Rats; Rats, Sprague-Dawley; Vasoconstrictor Agents

Exposure of rats to hyperoxia before organ harvesting protected their isolated hearts against global ischaemia-reperfusion injury in a previous study. The present study investigates whether hyperoxia influences vasomotor function and regional ischaemia of the heart. Isolated rings of the thoracic aorta were obtained from rats immediately or 24 h after in vivo exposure to 60 min of hyperoxia (>95% O2), and the in vitro dose-response to phenylephrine (PHE), prostaglandin F2alpha (PGF2alpha) and endothelin-1 (ET-1), acetylcholine (Ach) and sodium nitroprusside (SNP) was assessed. Hyperoxia in vivo increased the relaxation of aortic rings to Ach and SNP, while it delayed contraction to PHE. The effect was more evident when the vessels were harvested immediately rather than 24 h after hyperoxic exposure. In separate experiments rat hearts were isolated immediately after hyperoxia, buffer-perfused, and subjected to 30 min of regional ischaemia and reperfused for 120 min. Infarct size was determined by triphenyl tetrazolium chloride staining. Hyperoxia significantly reduced infarct size. In normoxic controls 23.0 +/- 8.3% of the area at risk was infarcted, while in hyperoxic animals infarct size was 14.8 +/- 5.6% of the area at risk (P = 0.012). Exposure of rats to hyperoxia modifies the vasomotor response of isolated aortic rings, and reduces the infarct size of isolated rat heart. These novel aspects of hyperoxic treatment require further studies to explore the potential of its clinical application.

Topics: Animals; Aorta, Thoracic; Blood Pressure; Coronary Circulation; Dinoprost; Endothelin-1; Heart Rate; Hyperoxia; Male; Myocardial Infarction; Nitroprusside; Phenylephrine; Rats; Rats, Sprague-Dawley; Rats, Wistar; Vasoconstriction; Vasodilation; Vasodilator Agents; Ventricular Function

To compare the effects of dexamethasone (Dex) and celecoxib (Cel) on F-isoprostane, prostacyclin (PGI2), and thromboxane A2 (TxA2) following hyperoxia, and hyperoxia followed by recovery in room air (RA), newborn rabbits were exposed to hyperoxia (80-100% oxygen) for 4 days, during which they were treated with saline (Sal, i.m.), Dex (i.m.), vehicle (Veh, PO), or Cel (PO, n = 12 per group). Six animals in each group were sacrificed immediately following hyperoxia, and the remainder allowed to recover in RA for 5 days. The control litters were treated simultaneously in RA with all conditions other than atmospheric oxygen being identical. Blood samples were assayed for 8-epi-prostaglandin F2alpha (8-epi-PGF2alpha), 6-keto prostaglandin F1alpha (6-ketoPGF1alpha), and TxB2. Dex and Cel decreased 8-epi-PGF2alpha during hyperoxia and the recovery period. Dex increased 6-ketoPGF2alpha following hyperoxia, while similar increments were noted during recovery with Cel. Although TxB2 was decreased only during the recovery period, TxB2/6-ketoPGF1alpha ratio was lower during hyperoxia and recovery in both treated groups. The effect of Cel on 8-epi-PGF2. and TxA2/PGI2 ratio confirm the formation of a COX-derived F2-isoprostane that is possibly linked to TxA2 receptors. Further studies are required to examine whether Cel can be used as a therapeutic alternative to Dex for oxygen-induced injury in the newborn.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Animals, Newborn; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Celecoxib; Dexamethasone; Dinoprost; Epoprostenol; F2-Isoprostanes; Hyperoxia; Oxidative Stress; Pyrazoles; Rabbits; Sulfonamides; Thromboxane B2

Oxygen exposure for a sufficient duration at high partial pressure results in pulmonary edema in humans and animals. Although the specific mediators of oxygen toxicity are unknown, evidence suggests that oxygen-based radicals such as superoxide anion (O2.) are increased in the lungs in the presence of hyperoxia and contribute to this injury. A series of isomeric prostanoid compounds, the isoprostanes, are formed by the free radical-initiated lipid peroxidation of arachidonic acid (AA). One of these isomers, 8-iso-PGF2alpha, is elevated in the bronchial alveolar lavage fluid of rats exposed to 90% oxygen for 48 h and is associated with a significant increase in protein accumulation in the pulmonary extravascular space. Alveolar macrophages (AMs) are capable of producing large quantities of (O2.), suggesting a role in pulmonary oxygen toxicity. We hypothesized that isolated rat AMs exposed to hyperoxia generate increased amount of 8-iso-PGF2alpha. AMs were exposed to air or 90% oxygen for 6, 12, 24, 48, 72, 96, and 120 h in the absence and presence of AA and/or calcium ionophore (A23187) and 8-iso-PGF2alpha was measured in the culture media. Exposure of primary cultures of AMs to 90% oxygen resulted in a significant increase in 8-iso-PGF2alpha in the media (25 +/- 2 pg/mL) compared with air-exposed controls (14 +/- 1 pg/mL). The addition of 10 microM AA and 2 microM A23187 to the culture media resulted in a marked increase in 8-iso-PGF2alpha production by AMs exposed to air and 90% oxygen. However, treatment of AMs with the combination of AA and A23187, followed by exposure to 90% oxygen for 72 h, resulted in a 27-fold increase in 8-iso-PGF2alpha compared with media alone and 90% oxygen. AMs metabolized free and phospholipid-bound AA to 8-iso-PGF2alpha, an activity enhanced in the 90% oxygen environment. Finally, acetylsalicylic acid, a cyclooxygenase inhibitor and free radical scavenger, reduced but did not abolish production of 8-iso-PGF2alpha. This study provides evidence that AMs produce a free radical-mediated isomeric prostaglandin compound that may be involved in pulmonary oxygen toxicity.

Topics: Animals; Arachidonic Acid; Bronchoalveolar Lavage Fluid; Calcimycin; Cells, Cultured; Dinoprost; F2-Isoprostanes; Hyperoxia; Kinetics; Macrophages, Alveolar; Male; Oxygen; Rats; Superoxides

We have previously reported that prostaglandin(PG) E2 levels in sheep cerebrospinal fluid (CSF) are high prenatally and abate rapidly after birth. This event may contribute to the establishment of continuous breathing. To explain this change, we have examined PG disposal mechanisms in the perinatal and adult (pregnant and non-pregnant animal) sheep brain by measuring the capacity of the isolated choroid plexus to concentrate [3H]PGF2alpha and [3H]PGE2. At 0.9 gestation, [3H]PGF2alpha uptake (expressed as the tissue-to-medium ratio, T/M) attained a steady-state by 15 min and was maintained thereafter (T/M at 60 min, 5.6 +/- 0.6; n = 16). Likewise, [3H]PGE2 was taken up by the tissue, but the actual accumulation was smaller (T/M at 60 min, 2.6 +/- 0.2; n = 8). Thin-layer radiochromatographic analysis of the tissue following incubation with [3H]PGF2alpha showed that 55 +/- 4% (n = 10) of radioactivity migrated as the 15-keto-13,14-dihydro metabolite. [3H]PGF2alpha uptake decreased upon treatment with probenecid (1 mM) (T/M, 2.5 +/- 0.2; n = 10) or after adding unlabelled PGF2alpha to the medium (1-60 microM) (T/M at 60 microM, 1.8 +/- 0.1; n = 13). The yield of labelled metabolite was also lower when using excess PGF2alpha (14% of control at 60 microM; n = 13), while it was not affected by probenecid. Uptake of both PGs did not change through development, from 0.7 gestation to day 18 postnatal, and attained higher values in the pregnant adult. Conversely, PGF2alpha catabolism decreased postnatally and became negligible by adult age. We conclude that during the perinatal period PGs can be removed from CSF by two distinct processes in the choroid plexus, active transport and catabolism. Neither process, however, can account for the birth-related change in CSF PGE2.

Topics: Aging; Animals; Animals, Newborn; Biological Transport; Choroid Plexus; Dinoprost; Dinoprostone; Embryonic and Fetal Development; Female; Gestational Age; Hyperoxia; Kinetics; Pregnancy; Probenecid; Prostaglandins; Reference Values; Sheep; Sucrose