Prostaglandins and thromboxane outflow from the perfused mesenteric vascular bed in spontaneously hypertensive rats

To clarify the metabolism of PGE2, prostacyclin (PGI2) and thromboxane A2 (TxA2) in small vessels in spontaneously hypertensive rats (SHR), we removed superior mesenteric vascular beds from 10 week old SHR and age matched normotensive controls (WKY). The mesenteric artery was perfused with Krebs-Henseleit buffer and samples of effluent collected every 15 minutes during 3 hours perfusion for analysis of PGE2, 6-keto-PGF1 alpha (a stable metabolite of PGI2) and TxB2 (a stable metabolite of TxA2) by specific radioimmunoassays. Levels of all three arachidonic acid (AA) metabolites, PGE2, 6-keto-PGF1 alpha and TxB2, in the mesenteric effluent were significantly reduced in SHR as compared to WKY. TxB2 was detected in all samples throughout the perfusion. 6-keto-PGF1 alpha/PGE2 ratios and TxB2/PGE2 ratios were significantly increased in SHR. 6-keto-PGF1 alpha/TxB2 ratios in the first four samples were significantly decreased in SHR as compared to WKY. These data suggest that there may be reduced availability of PG precusor AA and unbalanced synthesis of PGs in small vessels in SHR. Both may have relevance to the development of hypertension in the animals.     

The effect of hypoxia on rat splanchnic prostanoid output

The effect of hypoxia on isolated perfused rat mesenteric basal venous prostanoid output was studied. Male rat splanchnic vasculature was removed without (SV) or with its end organ (SV + SI) and perfused with Krebs' buffer with a pO2 of 460 or 60 mm torr. Basal splanchnic venous effluent was assayed for 6-keto-PGF1 alpha, TxB2 and PGE by radioimmunoassay at 30, 60, 120 and 180 min of perfusion. Basal output of SV 6-keto-PGF1 alpha was five and ten fold higher than for PGE and TxB2 respectively and comprised 36% or greater of SV + SI 6-keto-PGF1 alpha output. SV PGE and TxB2 output comprised less than 19 and 12% respectively of SV + SI output. Hypoxia decreased SV + SI PG output, 6-keto-PGF1 alpha being most affected. Hypoxia did not alter SV 6-keto-PGF1 alpha output indicating the SI as the anatomic location most influenced by hypoxia. The relative amounts of distribution of PGE or TxB2 output were not altered by hypoxia. These data suggest that there are two distinct areas of splanchnic prostanoid output, the SV and the SI. Decreased 6-keto-PGF1 alpha output might alter splanchnic blood flow at two levels, the splanchnic vasculature, and/or within the bowel wall.     

Dose-dependent effects of a pyridoquinazoline thromboxane synthetase inhibitor on arachidonic acid metabolites and hemodynamics during E. coli endotoxemia in anesthetized sheep

We investigated the effects of a new pyridoquinazoline thromboxane synthetase inhibitor infused before administering Escherichia Coli endotoxin into 18 anesthetized sheep with lung lymph fistulas. In normal sheep increasing plasma Ro 23-3423 concentrations were associated with increased plasma levels of 6-keto-PGF1 alpha, a reduced systemic vascular resistance (SVR, r = -0.80) and systemic arterial pressure (SAP, r = -0.92), the mean SAP falling from 80 to 50 mm Hg at the 20 and 30 mg/kg doses. Endotoxin infused into normal sheep caused transient pulmonary vasoconstriction associated with increased TxB2 and 6-keto-PGF1 alpha levels while vasoconstriction and TxB2 increase were significantly inhibited by pretreatment with Ro 23-3423 in a dose-dependent manner. When compared to controls, plasma and lymph levels of 6-keto-PGF1 alpha, PGF2 alpha and PGE2 after endotoxin infusion were increased several-fold by administering Ro 23-3423 up to plasma levels of 10 micrograms/ml. Doses over 30 mg/kg with blood levels above 10 micrograms/ml reduced plasma and lymph levels of 6-keto-PGF1 alpha, PGF2 alpha and PGE2, suggesting cyclooxygenase blockade at this dose. The peak 6-keto-PGF1 alpha levels at 60 min after endotoxin infusion in sheep with Ro-23-3423 levels below 10 micrograms/ml were associated with the greatest systemic hypotension due to a reduced SVR (r = -0.86). After endotoxin infusion the leukotrienes B4, C4, D4 and E4 in lung lymph were assayed by radioimmunoassay and high pressure liquid chromatography and remained at baseline values.     

Measurement of 6-keto-PGF1 alpha and thromboxane B2 levels in critically ill surgical patients

Systemic arterial and mixed venous plasma concentrations of 6-keto-PGF1 alpha and TxB2 were measured by radioimmunoassay in 63 critically ill patients with major trauma (n = 20) or sepsis (n = 43). Patients undergoing elective catheterization procedures served as controls (n = 10). Arterial and mixed venous 6-keto-PGF1 alpha and TxB2 levels were significantly elevated in patients with recent major trauma or active sepsis. The 6-keto-PGF1 alpha levels were found to be significantly elevated in the non-survivors and in patients with hepatic failure. The presence of severe pulmonary failure was not associated with increased levels of either 6-keto-PGF1 alpha or TxB2. Comparison of arterial and mixed plasma samples did not demonstrate increased pulmonary release of either compound. Increased eicosanoid production may account, in part, for the local vascular and humoral responses to tissue injury or infection.     

Neonatal urinary prostanoid excretion

Urinary excretion of prostanoids prostaglandin E2 (PGE2), PGE-M (7alpha-hydroxy-5,11-diketo-2,3,4,5,20-penta-19-carboxyprostano ic acid), 6-keto-PGF1alpha, 2,3-dinor-6-keto-PGF1alpha, thromboxane B2 (TxB2) 2,3-dinor-TxB2 and 11-dehydro-TxB2 was determined by gas chromatography/mass spectrometry in preterm and term infants to show that there is an age-dependent excretion rate of the above prostanoids in infants this young. Group I included premature children with normal postnatal development, Groups II and III included term children who were admitted in the neonatal period for observation because of feeding problems but who were subsequently found to be completely healthy. We present normal data of three primary prostanoids and four prostanoid metabolites. In Group I, excretion rates of 2,3-dinor-TxB2 were significantly lower than in Group II (P = 0.04) and in Group III (P = 0.05). Furthermore, the excretion rate of 11-dehydro-TxB2 in group I was significantly lower than in Group II (P = 0.05). We found no significant age-dependent differences between the three groups in excretion rates of PGE2, PGE-M, 6-keto-PGF1alpha, 2,3-dinor-6-keto-PGF1alpha, and TxB2.     

Bile duct ligation induced acute inflammation up-regulates cyclooxygenase-2 content and PGE2 release in guinea pig gallbladder smooth muscle cell cultures

INTRODUCTION: This study examines hypotheses that BDL induces increased guinea pig gallbladder smooth muscle PGE2 release by up-regulation of COX-2. METHODS: BDL, Sham and Control Hartley guinea pig gallbladders were placed in cell culture, grown to confluence and underwent Western Blot analysis for smooth muscle cell content of COX-1, COX-2, Prostacylin Synthase, actin, caldesmon, vinculin, meta-vinculin and tropomyosin and were assayed for basal release of 6-keto-PGF(1alpha), PGE2 and TxB2 by EIA. RESULTS: BDL did not alter content of smooth muscle cytoskeletal proteins. BDL for 48 h increased smooth muscle cell release of PGE2 and 6-keto-PGF(1alpha) by 3-fold or more when compared to the Control and Sham groups. Western Blot analysis showed increased content of COX-2 in the BDL group. CONCLUSIONS: BDL for 48 h markedly increased endogenous guinea pig smooth muscle cell PG release, which was due to increased COX-2 synthesis.     

Release of arachidonic acid metabolites from isolated human alveolar type II cells.

Human alveolar type II cells are thought to play a role in the pathogenesis of lung injury. Patterns of mediator release of arachidonic acid metabolism by type II cells were therefore studied after challenge with calcium ionophore A23187, opsonized zymosan and hydrogen peroxide. A time- and concentration dependent release of cyclooxygenase products was observed, with release of PGE2 greater than 6-keto-PGF1 alpha greater than TxB2. Addition of glutathione or bicarbonate further increased the production of PGE2. N-ethylmaleimide, a sulfhydryl (SH) reactant, induced a dose-dependent increase in the release of TxB2 and 6-keto-PGF1 alpha, but not of PGE2. This relates most likely to the SH-dependency and glutathione requirement of the PGE2 isomerase and SH-independence of thromboxane and prostacyclin isomerase.     

Eicosanoid balance and perfusion redistribution of oleic acid-induced acute lung injury.

We have proposed that endogenous prostacyclin opposes the vasoconstriction responsible for redistribution of regional pulmonary blood flow (rPBF) away from areas of increased regional lung water concentration (rLWC) in canine oleic acid- (OA) induced acute lung injury (D. P. Schuster and J. Haller. J. Appl. Physiol. 69: 353-361, 1990). To test this hypothesis, we related regional lung tissue concentrations of 6-ketoprostaglandin (PG) F1 alpha and thromboxane (Tx) B2 in tissue samples obtained 2.5 h after administration of OA (0.08 ml/kg iv) to rPBF and rLWC measured by positron emission tomography. After OA only (n = 16), rLWC increased in dependent lung regions. Some animals responded to increased rLWC by redistribution of rPBF away from the most edematous regions (OA-R, n = 6), whereas others did not (OA-NR, n = 10). In another six animals, meclofenamate was administered after OA (OA-meclo). After OA, tissue concentrations of 6-keto-PGF1 alpha were greater than TxB2 in all groups, but concentrations of 6-keto-PGF1 alpha were not different between OA-R and OA-NR animals. TxB2 was increased in the dependent regions of animals in both OA-R and OA-NR groups compared with controls (no OA, n = 4, P < 0.05). The tissue TxB2/6-keto-PGF1 alpha ratio was smaller in controls and OA-NR in which no perfusion redistribution occurred than in OA-R and OA-meclo in which it did occur. This TxB2/6-keto-PGF1 alpha ratio correlated significantly with the magnitude of perfusion redistribution.(ABSTRACT TRUNCATED AT 250 WORDS)     

Basal prostaglandin synthesis by the isolated perfused rat kidney

In order to assess the main characteristics of the prostaglandin (PG) biosynthesis by the isolated perfused rat kidney, the urinary and venous outputs of PGE2, PGF2alpha, 6-keto-PGF1alpha and of thromboxane (Tx)B2 were followed during 120 min after an equilibration period of 30 min. Single pass kidneys were perfused with a Krebs-Henseleit solution added with Polygeline at a constant flow rate providing a perfusion pressure about 90 mm Hg. From the beginning of the study, major differences could be observed in the renal biosynthetic rate of the 4 PG studied which were mainly excreted into the venous effluent. During the perfusion, urinary and venous outputs of PGE2, PGF2alpha and of TxB2 remained stable whereas those of 6-keto-PGF1alpha sharply increased and were found inversely related to the glomerular filtration rate (r = -0.95; p n 0.001). Finally, the urinary and venous outputs of each of the four PGs studied were found positively related. It is concluded that the isolated perfused rat kidney is a valuable preparation for studying the biosynthesis of PGs and that, at least in thi model, the urinary excretion of PGs is a good index of their renal synthesis.     

Comparison of plasma prostanoid levels in the human cord artery in normal and fetal distressed deliveries

Prostaglandin E2 (PGE2), thromboxane B2 (TXB2; as a stable metabolite of TXA2), prostaglandin F2 alpha (PGF2 alpha) and 6-keto-PGF1 alpha (as a stable end product of prostacyclin) have been measured by using specific radioimmunoassay in the plasma of the cord artery immediately after delivery before the cord was clamped. Plasma prostanoid concentrations in normal deliveries (n = 8, as controls) were 24.8 +/- 2.6 (PGE2), 246.8 +/- 37.0 (TXB2), 122.2 +/- 13.3 (PGF2 alpha) and 82.1 +/- 7.7 (6-keto-PGF1 alpha) respectively (pg/ml, mean +/- s.e). On the other hand, in fetal distressed deliveries showing continuous bradycardia (n = 6), they increased significantly to 275.4 +/- 20.1 (PGE2), 948.6 +/- 102.5 (TXB2), 218.0 +/- 21.4 (PGF2 alpha) and 1498.6 +/- 298.4 (6-keto-PGF1 alpha) respectively (pg/ml, mean +/- s.e, p less than 0.005). However, both PGF2 alpha/PGE2 and TXB2/6-keto-PGF1 alpha ratios declined significantly from 4.70 +/- 0.33 to 0.68 +/- 0.05 and from 3.07 +/- 0.37 to 0.68 +/- 0.12 respectively (mean +/- s.e, p less than 0.005) in the fetal distressed group compared with those of the controls. From these results, it may be concluded that the cord artery, which is known as the patent source for the production of PGE2 and prostacyclin, did exert a sufficiently strong reaction to overcome the undesirable haemodynamic changes to maintain the fetal well-being in utero.     

The relation between thromboxane and prostaglandin synthesis in human decidua tissue: a comparison of eicosanoid synthesis in minced tissue with that in a cell-free preparation

Radiotracer studies and radioimmunoassay measurements demonstrate that minced tissues of human decidua produce chiefly thromboxane B2 (TxB2) (70% of total eicosanoids) and small amounts of prostaglandin F2 alpha (PGF2 alpha) (13%) PGD2 (8%), 6-keto-PGF1 alpha (5%) and PGE2 (4%). Inhibition of thromboxane synthesis with a specific inhibitor (OKY-1581: sodium (E)-3-[4(-3-pyridylmethyl)-phenyl]-2-methyl propenoate) increased prostaglandin formation in general, with the main product being PGF2 alpha (38%), a nonenzymic derivative of PGH2. Crude particulate fractions prepared from the same tissue synthesized two major products from [3H]arachidonate, TxB2 and 6-keto-PGF1 alpha (54 and 30%, respectively) and some PGF2 alpha and PGE2 (8-8%). However, in the presence of reduced glutathione (GSH), PGE2 became the main product (81%) (TxB2, 15%; PGF2 alpha, 2%; and 6-keto-PGF1 alpha, 2%). Half-maximal stimulation of PGE2 synthesis occurred at 46 microM GSH. The GSH concentration of tissue samples was found to be 110 +/- 30 microM. We conclude that human first trimester decidua cells possess the key enzymes of prostaglandin and thromboxane synthesis. Apparently, the production of these compounds is controlled by a specific mechanism in the tissue, which keeps PGE and prostacyclin synthesis in a reversibly suppressed state, whereas the formation of thromboxane is relatively stimulated.     

Distribution of cyclooxygenase products with cyclooxygenase inhibition in isolated dog lung

Arachidonic acid metabolism can lead to synthesis of cyclooxygenase products in the lung as indicated by measurement of such products in the perfusate of isolated lungs perfused with a salt solution. However, a reduction in levels of cyclooxygenase products in the perfusate may not accurately reflect the inhibition of levels of such products as measured in lung parenchyma. We infused sodium arachidonate into the pulmonary circulation of isolated dog lungs perfused with a salt solution and measured parenchymal, as well as perfusate, levels of 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), prostaglandin F2 alpha (PGF2 alpha), prostaglandin E2 (PGE2), and thromboxane B2 (TxB2). These studies were repeated with indomethacin (a cyclooxygenase enzyme inhibitor) in the perfusate. We found that indomethacin leads to a marked reduction in perfusate levels of PGF2 alpha, PGE2, 6-keto-PGF1 alpha, and TxB2, as well as a marked reduction in parenchymal levels of 6-keto-PGF1 alpha and TxB2 when parenchymal levels of PGF2 alpha and PGE2 are not reduced. We conclude that, with some cyclooxygenase products, a reduction in levels of these products in the perfusate of isolated lungs may not indicate inhibition of levels of these products in the lung parenchyma and that a reduction in one parenchymal product may not predict the reduction of other parenchymal products. It can be speculated that some of the physiological actions of indomethacin in isolated lungs may result from incomplete or selective inhibition of synthesis of pulmonary cyclooxygenase products.     

Urinary prostaglandin excretion in pregnancy: the effect of dietary sodium restriction

INTRODUCTION: Dietary sodium restriction results in activation of the renin-angiotensin-aldosterone-system. In the non-pregnant situation renin release in response to a low sodium diet is mediated by prostaglandins. We studied the effect of dietary sodium restriction on urinary prostaglandin metabolism in pregnancy. PATIENTS AND METHODS: In a randomized, longitudinal study the excretion of urinary metabolites of prostacyclin (6-keto-PGF(1 alpha)and 2,3-dinor-6-keto-PGF(1 alpha)) and thromboxane A(2)(TxB(2)and 2,3-dinor-TxB(2)) was determined throughout pregnancy and post partum in 12 women on a low sodium diet and in 12 controls. RESULTS: In pregnancy the excretion of all urinary prostaglandins is increased. The 6-keto-PGF(1 alpha)/ TxB(2)-ratio as well as the 2, 3-dinor-6-keto-PGF(1 alpha)/ 2,3-dinor-TxB(2)-ratio did not significantly change in pregnancy. CONCLUISION Prostacyclin and thromboxane do not seem to play an important role in sodium balance during pregnancy.     

Uteroplacental production of eicosanoids in ovine pregnancy

Dramatic cardiovascular alterations occur during normal ovine pregnancy which may be associated with increased prostaglandin production, especially of uteroplacental origin. To study this, we examined (Exp 1) the relationships between cardiovascular alterations, e.g., the rise in uterine blood flow and fall in systemic vascular resistance, and arterial concentrations of prostaglandin metabolites (PGEM, PGFM and 6-keto-PGF1 alpha) in nonpregnant (n = 4) and pregnant (n = 8) ewes. To determine the potential utero-placental contribution of these eicosanoids in pregnancy, we also studied (Exp 2) the relationship between uterine blood flow and the uterine venous-arterial concentration differences of PGE2, PGF2 alpha, PGFM, 6-keto-PGF1 alpha, and TxB2 in twelve additional late pregnant ewes. Pregnancy was associated with a 37-fold increase in uterine blood flow and a proportionate (27-fold) fall in uterine vascular resistance (p less than 0.01). Arterial concentrations of PGEM were similar in nonpregnant and pregnant ewes (316 +/- 19 and 245 +/- 38 pg/ml), while levels of PGFM and PGI2 metabolite 6-keto-PGF1 alpha were elevated 23-fold (31 +/- 14 to 708 +/- 244 pg/ml) and 14-fold (12 +/- 4 to 163 +/- 78 pg/ml), respectively (p less than 0.01). Higher uterine venous versus uterine arterial concentrations were observed for PGE2 (397 +/- 36 and 293 +/- 22 pg/ml) and 6-keto-PGF1 alpha (269 +/- 32 and 204 +/- 32 pg/ml), p less than 0.05, but not PGF2 alpha or TxB2. Although PGFM concentrations appeared to be greater in uterine venous (1197 +/- 225 pg/ml) as compared to uterine arterial (738 +/- 150 pg/ml) plasma, this did not reach significance (0.05 less than p less than 0.1). In normal ovine pregnancy arterial levels of PGI2 are increased, which may in part reflect increased uteroplacental production. Moreover the gravid ovine uterus also appears to produce PGE2 and metabolize PGF2 alpha.     

Modulation of prostanoid formation by various polyunsaturated fatty acids during platelet-endothelial cell interactions

Previous studies have reported that polyunsaturated fatty acids (PUFAs) of nutritional interest may influence arachidonic acid (20:4n-6) metabolism in both platelets and endothelium, when tested separately. In the present study, platelets (PL) and cultured endothelial cells (EC) were first pre-enriched with eight different PUFAs for a two hour incubation in the presence of free fatty acid albumin pre-coated with each acid. EC, PL or both cell populations in combination, were then stimulated by thrombin (0.1 U/ml) for five minutes. Prostanoids were extracted, purified by thin-layer chromatography, and TxB2, 6-keto-PGF1 alpha and PGE2 were quantitated by radioimmunoassays. Prostanoids or dihomoprostanoids formed from cyclooxygenase substrates other than 20:4n-6 were measured by gas chromatography-negative chemical ionisation mass-spectrometry (GC-MS). When co-incubated with EC, PL produced less TxB2 (-15 and -85% in the absence and presence of thrombin, respectively). In contrast, 6-keto-PGF1 alpha increased by 189 (basal conditions) and 358% (thrombin stimulation) when PL were added to EC, in agreement with PGH2 transfers from PL to EC. PGE2, produced by both cell populations, reached amounts which roughly represent the sum of those measured in PL and EC alone, except when cells were pre-enriched with linoleic (18:2n-6) and the n-3 family fatty acids (18:3-, 20:5- and 22:6n-3). 6-keto-PGF1 alpha was markedly inhibited by adrenic acid (22:4n-6), while this acid was converted into dihomo-6-keto-PGF1 alpha, the stable metabolite of dihomoprostacyclin. 22:4n-6 also inhibited TxB2 formation and was converted into dihomo-TxA2.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of carnitine and its congeners on eicosanoid discharge from rat cells: implications for release of TNFalpha

THE acyl carrier coenzyme A (CoA) is involved in fatty acid metabolism. The carnitine/CoA ratio is of particular importance in regulating the transport of long-chain fatty acids into mitochondria for oxidation. Also CoA has a role in the formation and breakdown of products from both the cyclooxygenase and lipoxygenase pathways of the precursor arachidonic acid. In the present study the effect of 4 days feeding of 300 mg/kg/day of L-carnitine, acetyl Lcarnitine and propionyl L-carnitine on the basal and calcium ionophore (A23187) stimulated release of arachidonic acid metabolites from rat carrageenin elicited peritoneal cells was investigated. There were two series of experiments carried out. In the first, the harvested peritoneal cell population consisted of less than 90% macrophages and additional polymorphonuclear (PMN) leucocytes. The basal release of prostaglandin E(2) (PGE(2)), 6-ketoprostaglandin F(1alpha) (6-keto-PGF(1alpha)) and leukotriene B(4) (LTB(4)) was stimulated by all treatments. The A23187 stimulated release of 6-keto-PGF(1alpha) and LTB(4) was increased by all three compounds. The 6-keto-PGF(1alpha):TxB(2) and 6-keto-PGF(1alpha):LTB(4) ratios were increased by carnitine treatment. These results suggested that carnitine could modify the macrophage component of an inflammatory site in vivo. In the second series of experiments the harvested cell population was highly purified (>95% macrophages) and none of the compounds fed to the rats caused a change of either eicosanoid or TNFalpha formation. Moreover the 6-keto-PGF(1alpha):TxB(2) and 6-keto-PGF(1alpha):LTB(4) ratios were not enhanced by any of the compounds tested. It is conceivable that in the first series the increased ratios 6-keto-PGF(1alpha):TxB(2) and 6-keto-PGF(1alpha):LTB(4) reflected the effect of carnitine or its congeners on PMN leucocytes rather than on macrophages.     

Prostanoids in bronchoalveolar lavage fluid do not predict outcome in congenital diaphragmatic hernia patients

Vasoactive prostanoids may be involved in persistent pulmonary hypertension (PPH) in infants with a congenital diaphragmatic hernia (CDH). We hypothesized that increased levels of prostanoids in bronchoalveolar lavage (BAL) fluid would predict clinical outcome. We measured the concentrations of 6-keto-prostaglandin F(1alpha) (6-keto-PGF(1alpha)), thromboxane B(2) (TxB(2)), protein, albumin, total cell count, and elastase-alpha1-proteinase-inhibitor complex in BAL fluid of 18 CDH patients and of 13 control subjects without PPH. We found different concentrations of prostanoids in BAL fluid of CDH patients with PPH: infants with a poor prognosis had either high levels of both 6-keto-PGF(1alpha) and TxB(2) compared to controls, or high levels of 6-keto-PGF(1alpha) only. TxB(2) levels showed a large variability in all CDH patients irrespective of outcome. We conclude that prostanoid levels in BAL fluid do not predict clinical outcome in CDH patients.     

Cholecystokinin (CCK) down regulates PGE2 and PGI2 release in inflamed Guinea pig gallbladder smooth muscle cell cultures

This study examines the hypothesis that cholecystitis down-regulates Guinea pig gallbladder (GPGB) smooth muscle cholecystokinin (CCK)-stimulated prostaglandin (PG) release. Guinea pig gallbladder from Control and 48 h bile duct ligated (BDL) animals were placed in cell culture and grown to confluence. The cultures underwent Western Blot analysis for smooth muscle cell content of COX-1, COX-2, Prostacyclin Synthase (PS), or were incubated with CCK at 10(-8)M or 10(-6)M with and without indomethacin for 1h and analyzed for release of 6-keto-PGF1alpha, PGE2 and TxB2 by EIA. BDL increased Guinea pig gallbladder cell culture basal PGE2 and PGI2 release which was in part due to increased COX-2 content. CCK incubation down-regulated BDL Guinea pig gallbladder cell culture release of 6-keto-PGF1alpha and PGE2 and down-regulated COX-2 content but did not alter the Control group. The decrease in CCK-mediated BDL cell Guinea pig gallbladder release may be an endogenous mechanism to limit physiologic derangements induced by increased endogenous gallbladder PG synthesis during early acute cholecystitis.     

Lung eicosanoids in perinatal rats with congenital diaphragmatic hernia

Abnormal levels of pulmonary eicosanoids have been reported in infants with persistent pulmonary hypertension (PPH) and congenital diaphragmatic hernia (CDH). We hypothesized that a dysbalance of vasoconstrictive and vasodilatory eicosanoids is involved in PPH in CDH patients. The levels of several eicosanoids in lung homogenates and in bronchoalveolar lavage fluid of controls and rats with CDH were measured after caesarean section or spontaneous birth. In controls the concentration of the stable metabolite of prostacyclin (6-keto-PGF(1alpha)), thromboxane A(2) (TxB(2)), prostaglandin E(2) (PGE(2)), and leukotriene B(4) (LTB(4)) decreased after spontaneous birth. CDH pups showed respiratory insufficiency directly after birth. Their lungs had higher levels of 6- keto-PGF(1alpha), reflecting the pulmonary vasodilator prostacyclin (PGI(2)), than those of controls. We conclude that in CDH abnormal lung eicosanoid levels are present perinatally. The elevated levels of 6-keto-PGF(1alpha) in CDH may reflect a compensation mechanism for increased vascular resistance.     

Plasma 6-keto-PGF1 alpha, thromboxane B2 and PGE2 during diabetic ketoacidosis

In 10 patients admitted to hospital with diabetic ketoacidosis plasma prostanoids 6-keto-PGF alpha, thromboxane B2 and PGE2 were studied before treatment and following recovery. During ketoacidosis the median plasma 6-keto-PGF1 alpha and PGE2 were significantly increased compared to those of a normal reference group: 5.2 pg/ml and 3.9 pg/ml versus 1.7 pg/ml and 0.4 pg/ml (p less than 0.01 and p less than 0.05). In response to therapy both prostanoids decreased significantly towards a normal level, 6-keto-PGF1 alpha: 0.5 pg/ml p less than 0.01 and PGE2: 0.08 p less than 0.05 respectively. The changes in plasma 6-keto-PGF1 alpha were negatively correlated to changes in pH, rho: -0.7788 p = 0.0135, whereas the changes in PGE2 were positively correlated to serum creatinine at admittance, rho: 0.6976, p = 0.0368 and to the amount of intravenous fluid and insulin used during treatment, rho: 0.7500 p = 0.0126 and rho: 0.8424, p = 0.0023 respectively. Plasma thromboxane B2 concentrations were not elevated and did not change after treatment of the ketoacidosis.