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1.
The production of vasodilatory, antiaggregatory prostacyclin (PGI2) and vasoconstrictory, proaggregatory thromboxane A2 (TxA2) by the placenta was studied in the cases of hypertensive pregnancy complications by superfusing pieces from maternal and fetal sides of placentae of 9 pre-eclamptic, 6 hypertensive and 11 healthy women and measuring the release of 6-keto-prostaglandin F (6-keto-PGF) and thromboxane B2 (TxB2), the breakdown products of PGI2 and TxA2 respectively, from the superfusate. Both sides of the placentae from the controls produced 6-keto-PGF (maternal side 0.5±0.1 ng/g/min dry weight of tissue, mean±SEM; fetal side 0.7±0.2 ng/g/min) and TxB2 (maternal side 2.5±0.4 ng/g/min; fetal side 2.7±0.5 ng/g/min with no correlation between the two. The 6-keto-PGF production was normal in hypertensive complications whereas the TxB2 production was increased on the fetal side of the placentae obtained from the pre-eclamptic (3.7±0.3 ng/g/min: p<0.05) and hypertensive women (4.1±0.4 ng/g/min; p<0.025). This may explain the occurrence of microthrombi and infarctions in placentae of hypertensive women.  相似文献   

2.
Human endometrium obtained from fresh hysterectomy specimens was perifused for 7 hr in 95% O2/5% CO2 at 37°C. The phase of the menstrual cycle was determined by histological examination. The concentrations of PGF, 6-keto-PGF and TxB2 in 20 min fractions of the perifusion medium were measured by radioimmunoassay and production rates were calculated in terms of dry weight of tissue. Biphasic patterns of production were observed; high initial values fell to about 20% at 2 hr and then increased to relatively stable values at about 4 hr which were maintained for the next 2 hr. During this latter period, production rates in endometria taken at different phases of the cycle differed markedly from each other; the production rates of PGF in secretory and early proliferative endometria were low (15.8 ± 2.6, mean ± SEM and 67.2 ± 8.3 ng/min/g respectively) whereas they were high in late proliferative and premenstrual endometria (188.0 ± 16.7 and 196.4 ± 16.9 ng/min/g respectively). The patterns of production of 6-keto-PGF and TxB2 were similar to those of PGF but the absolute values were much lower (<10%). We conclude that the observed rates of production of prostaglandins by perifused human endometrium are consistent with synthesis being stimulated either by estrogen or withdrawal of hormonal support and being inhibited by progesterone.  相似文献   

3.
PGI2 and 6-keto-PGF were converted to 6-methoxime-PGF (6-MeON-PGF) by treatment with methoxyamine HCl in acetate buffer. The formed 6-MeON-PGF was measured by radioimmunoassay. Antisera were raised in rabbits after immunization against 6-MeON-PGF-BSA conjugate. Diluted 1:20.000 to bind 50% of the tracer (3H-6-MeON-PGF, 100 Ci/mmol), the antiserum cross reacted 0.8% with PGE2, 1% with PGF and less than 0.2% with PGD2, PGF, PGF and TXB2. The radioimmunoassay was used to estimate release of PGI2 and 6-keto-PGF from chopped rabbit renal medulla and cortex incubated in Krebs-Ringer bicarbonate buffer (37°C, 30 min). The 6-keto-PGf radioimmunoassay was validated in biological samples by mass fragmentography. The chopped medulla (n=5) released 38±9 ng/g/min and the cortex (n=5) 4.7±2.0 ng/g/min, while the release of immunoreactive PGE2 (iPGE2) and iPGF was 171±26 and 74±13 ng/g/min from the medulla and 4.3±1.3 and 2.7±0.3 ng/g/min from the cortex, respectively. The results confirm previous findings, which indicate that in the renal medulla prostaglandin endoperoxides are mainly transformed to prostaglandins, while in the cortex transformation to PGI2 seems to be of greater importance.  相似文献   

4.
We have investigated the metabolism of [3]H-prostaglandin (PG)I2 and its non-enzymatic breakdown product [3]H-6-keto-PGF by rat pulmonary tissue and their possible uptake and metabolism upon passage through the isolated perfused rat lung. When incubated with rat lung homogenate in the presence of β-NAD, [3]H-PGI2 was extensively degraded into at least one metabolite, while [3]H-6-keto-PGF was only minimally metabolized. However, on passage through isolated perfused rat lungs, neither [3]H-PGI2 nor [3]H-6-keto-PGF were removed from the circulation into the lung or degraded. This demonstration that PGI2 is not a substrate for the transport system for the removal of PGs from the circulation into the lung further illustrates that this system is a critical determinant for the pulmonary inactivation of circulating prostaglandins. The experimental findings are discussed in reference to the structure-activity requirements necessary for pulmonary transport and subsequent metabolism.  相似文献   

5.
The rate constant for the hydrolysis of prostacyclin (PGI2) to 6-keto-PGF was measured by monitoring the UV spectral change, over a pH range 6 to 10 at 25°C and the total ionic strength of 0.5 M. The first-order rate constant (kobs) extrapolated to zero buffer concentration follows an expression, kobs = kH+ (H+), where kH+ is a second-order rate constant for the specific acid catalyzed hydrolysis. The value of kH+ obtained (3.71 × 104 sec−1 M−1) is estimated approximately 700-fold greater than a kH+ value expected from the hydrolysis of other vinyl ethers. Such an unusually high reactivity of PGI2 even for a vinyl ether is attributed to a possible ring strain release that would occur upon the rate controlling protonation of C5. A Brønsted slope (α) of 0.71 was obtained for the acid (including H3O+) catalytic constants, from which a pH independent first-order rate constant for the spontaneous hydrolysis (catalyzed by H2O as a general acid) was estimated to be 1.3 × 10−6 sec−1. An apparent activation energy (Ea) of 11.85 Kcal/mole was obtained for the hydrolysis at pH 7.48, from which a half-life of PGI2 at 4°C was estimated to be approximately 14.5 min. when the total phosphate concentration is 0.165 M (cf. 3.5 min. at 25°C).  相似文献   

6.
The cross-reactivity of the PGI3 metabolite, Δ17-6-keto-PGF, with antibodies against 6-keto-PGF for radioimmunoassays (RIA) has been investigated. Δ17-6-keto-PGF was obtained either from commercial sources or after its purification from endothelial cells. In the latter case, primary cultured bovine aortic endothelial cells were incubated for 20 min at 37°C with 10 μM eicosapentaenoic acid (EPA) in the presence of 2 μM 13-hydroperoxy-octadecadienoic acid, an activator of the EPA cyclooxygenation, and the 6-keto-PGF and Δ17-6keto-PGF produced were separated by RP-HPLC. Then, cross-reactivities of the commercial and purified Δ17-6-keto-PGF with 6-keto-PGF antibodies were determined and found not to exceed 10%. In addition, the amounts of prostacyclin-related compounds detected by direct measurements in media of cells loaded with EPA were compared with those obtained after purification of 6-keto-PGF. In accordance with the cross-reactivity data, we found that RIA in media mainly measured 6-keto-PGF, the Δ17-6-keto-PGF formed being undetected at 90%. It is concluded that 6-keto-PGF antibodies generally used for RIA of 6-keto-PGF are highly specific since they can discriminate a metabolite bearing an additional double bond such as the PGI3 metabolite Δ17-6-keto-PGF.  相似文献   

7.
Prostaglandins (PG)I2, PGE2 and 6-keto PGF1α were infused directly into the gastric arterial supply at 10−9, 10−8 and 10−7 g/kg/min during an intra-gastric artery pentagastrin infusion in anesthetized dogs. 6-keto PGF1α was also infused at 10−6 g/kg/min. Gastric arterial blood flow was measured continuously with a non-cannulating electromagnetic flow probe and gastric acid collected directly from the stomach. PGI2 and PGE2 produced similar dose-dependent increases in blood flow with an increase of more than four-fold at the highest dose. Both PGs inhibited acid output over this dose range with PGE2 having 10 times the potency of PGI2. 6-keto PGF1α was at least 1000 times less active than PGI2 or PGE2 at increasing blood flow and failed to inhibit acid output even at 10−6 g/kg/min.  相似文献   

8.
Prostaglandin(PG) I2 and its stable metabolite, 6-keto-PGF, were tested on the isolated ductus arteriosus from mature fetal lambs. PGI2 relaxed the ductus in high doses (threshold 10−6M) and its activity disappeared on standing at room temperature for 30 minutes. 6-keto-PGF was inactive at all doses. By contrast, PGE2 produced a dose-dependent relaxation over a range between 10−10 and 10−6 M. These findings confirm that PGE2 is the most potent ductal relaxant among the known derivatives of arachidonic acid. PGE2 probably maintains ductus patency in the fetus and, together with PGE1, remains the compound of choice in the management of newborns requiring a viable ductus for survival.  相似文献   

9.
Homogenates of eleven different blood vessels from normal Sprague-Dawley rats varied in their ability to produce PGI2 (i.e., 6-keto-PGF) from [1−14C]PGH2. The most notable difference was seen between arteries and veins. Arterial tissues produced more 6-keto-PGF from exogenous PGH2 than veins at all enzyme (i.e., protein) concentrations tested. Similar results were obtained utilizing different homogenization techniques or arterial and venous rings, indicating this difference was real and not due to homogenization artifacts. In addition, the thoracic segment of the inferior vena cava was more active in converting added [1−14C]PGH2 to 6-keto-PGF than the abdominal segment of added inferior vena cava suggestive of a possible segmental distribution of the enzyme activity in blood vessels. These results may be interpreted as indicating that PGI2 may have a vasomotor function for blood vessels in addition to its proposed antithrombotic role.  相似文献   

10.
A direct comparison of the relative potencies of the prostaglandins PGI2 and 6-kto-PGE1 to induce renin release was made in the isolated rat kidney, which was perfused with a synthetic medium at constant perfusion pressure.Both prostaglandins stimulated renin release in a dose-dependent manner (0.01 to 1 μM) and with equal potency.Also in the isolated rabbit kidney, PGI2 and 6-keto-PGE1 had the same potency to induce renin release at 1 μM final concentration.Following infusion of 6-keto-PGE1 a small increase of vascular resistance in the rat kidney was observed, whereas in the rabbit kidney no constrictor effect was seen.When perfusate of PGI2 or 6-keto-PGE1-infused rat kidneys were tested for antiaggregatory activity in the ADP induced aggregation of human platelets and compared with authentic standards, the results showed 6-keto-PGE1 passes the kidney essentially unchanged, whereas only 25–40% of the infused PGI2 appear in the venous perfusates, as judged from the recovery of antiaggregatory activity.Analysis of venous perfusates from 3H-PGI2 infused kidneys by high performance liquid chromatography indicates that about 25% of the infused PGI2 remains intact, a major portion of the perfused radioactivity was identified as 6-keto-PGF by combined gaschromatography-mass-spectrometry (19).We conclude that the renin-stimulating effect of PGI2 is not secondary to its metabolism to 6-keto-PGE1, as has been suggested in the literature (8).  相似文献   

11.
In the Tyrode's perfused rabbit kidney PGI2 (1.3 × 10−8-3.3 × 10−7M) dose-dependently inhibited vasoconstrictor responses to sympathetic nerve stimulation, as did PGE2. The dose-effect curve of the two compounds differed, making PGI2 the less potent in the low concentration and the more potent in the high. PGI2 also inhibited the vasoconstrictor response to exogenous noradrenaline, but it had no effect on transmitter release. The main metabolite of PGI2, 6-keto-PGF, was ineffective both on noradrenaline release and on vascular responses to nerve stimulation or exogenous noradrenaline. It is suggested that PGI2,if a significant renal prostaglandin, may modulate renal neuroeffector transmission post-junctionally, thereby forming a complement to the prejunctional action of PGE2.  相似文献   

12.
The metabolism of endogenous PGI2 (released by angiotensin II or bradykinin) and exogenous PGI2 by 15-hydroxy-PG-dehydrogenase and Δ13-reductase was studied in five different vascular beds of the anaesthetized cat. Plasma concentrations of 6-keto-PGF (the product of spontaneous hydrolysis of PGI2) and 6,15-diketo-13,14-dihydro-PGF (the metabolite formed from PGI2 by 15-hydroxy-PG-dehydrogenase and Δ13-reductase) were determined in the efferent vessels of the respective vascular beds by specific radioimmunoassays.No major metabolism of PGI2 by 15-hydroxy-PG-dehydrogenase and Δ13-reductase was detected in the head and the hindlimbs of the cat. In the lung exogenous (circulating) PGI2 was not metabolized, whereas PGI2 synthetized in the lung itself was converted to 6,15-diketo-13,14-dihydor-PGF. No significant amounts of 6,15-diketo-13,14-dihydro-PGF-immunoreactivity were detected in hepatic venous blood after infusion of PGI2 into the portal vein. However as also no 6-keto-PGF was found, the liver seems to efficiently extract PGI2 from the circulation. The cat kidney had the highest capacity of all vascular beds investigated to release endogenous and exogenous PGI2 as 6-15-diketo-13,14-dihydro-PGF. In other organs (vascular beds) investigated PGI2 is either metabolized less efficiently by the 15-hydroxy-PG-dehydrogenase or further transformed to other metabolites.  相似文献   

13.
Estrogen has been proposed as a negative risk factor for development of peripheral vascular disease yet mechanisms of this protection are not known. This study examines the hypothesis that estrogen stimulates rat aortic endothelial cell (RAEC) release of PGI2. Male Sprague-Dawley rat abdominal aortic 1-mm rings were placed on 35 mm matrigel plates, and incubated for 1 week. The cells were transferred to a Primaria 60-mm dish and maintained from passage 3 in RAEC complete media and experiments performed between passages 4–10. Cells were incubated with Krebs-Henseleit buffer (pH 7.4) containing carrier or increasing concentrations of β-estradiol or testosterone for 60 min. The effluent was analyzed for eicosanoid release of 6-keto-PGF (6-keto, PGI2 metabolite), PGE2 and thromboxane B2 (TXB2) by EIA (hormone stimulated — basal). Cells were analyzed for total protein by the Bradford method and for cyclooxygenase-1 (COX-1) and prostacyclin synthase (PS) content by Western blot analysis and densitometry. Testosterone did not alter RAEC 6-keto-PGF release, whereas estrogen increased RAEC 6-keto-PGF release in a dose-related manner. Estrogen preincubation (10 ng/ml) decreased COX-1 and PS content by 40% suggesting that the estrogen-induced increase in male RAEC PGI2 release was not due to increased synthesis of COX-1 or PS. These data support the hypothesis that estrogen stimulation can increase endogenous male RAEC release of PGI2.  相似文献   

14.
The role of prostacyclin (PGI2) on amphibian adrenal steroidogenesis was studied in perifused interrenal fragments from adult male frogs. Exogenous PGI2 (3×10−8 M to 3×10−5 M) and, in a lesser extent, 6-keto-PGF increased both corticosterone and aldosterone production in a dose-related manner. Short pulses (20 min) of 0.88 μM PGI2 administered at 90 min intervals within the same experiment did not induce any desensitization phenomenon. A prolonged administration (6 h) of PGI2 gave rise to an important increase in steroid production followed by a decline of corticosteroidogenesis. Indomethacin (IDM, 5 μM) induced a marked reduction of the spontaneous secretion of corticosteroid which confirmed the involvement of endogenous PGs in the process of corticosteroid biosynthesis. The IDM-induced blockade of corticosterone and aldosterone secretion was totally reversed by administration of exogenous PGI2 in our model. Angiotensin II (AII) induced a massive release of 6-keto-PGF, the stable metabolite of PGI2. The increase of 6-keto-PGF preceded the stimulation of corticosterone and aldosterone secretions. In contrast, the administration of ACTH did not modify the release of 6-keto-PGF. These results indicate that PGI2 might be an important mediator of adrenal steroidogenesis in frog. They confirm that the corticosteroidogenic actions of ACTH and AII are mediated by different mechanisms.  相似文献   

15.
The influence of intra-renal infusions of prostaglandin (PG) I2, PGE2 and PGD2 on renin secretion and renal blood flow was investigated in renally denervated, beta-adrenergic blocked, indomethacin treated dogs with unilateral nephrectomy. All three prostaglandins when infused at doses of 10−8 g/kg/min and 10−7 g/kg/min resulted in marked renal vasodilation. Renin secretory rates increased significantly with both PGI2 and PGE2 at the 10−8 g/kg/min and 10−7 g/kg/min infusion rates in a dose dependent manner. However, PGD2 was inactive. At 10−7 g/kg/min, PGI2 infusions resulted in systemic hypotension indicating recirculation of this prostaglandin. These findings suggest that PGI2 should be included among the cyclooxygenase derived metabolites of arachidonic acid to be considered as possible mediators of renin release.  相似文献   

16.
The pulmonary formation of prostacyclin (PGI2), as reflected by the difference in concentration of pulmonary and systematic arterial radioimmunoassayed 6-keto-PGF, was determined in six healthy waking subjects. The systematic arterial 6-keto-PGF levels were low (50 pg/ml), and no evidence of pulmonary formation and release of the compound was noted. In other experiments systemic arterial 6-keto-PGF levels were determined in patients prior to and during artificial ventilation, as well as during and after occlusion of the pulmonary circulation (extra-corporeal circulation, ECC). The arterial 6-keto-PGF concentration prior to artificial ventillation was 17±4 pg/ml, i.e. within the range observed in the healthy subjects. During artificial ventilation the arterial levels of 6-keto-PGF increased to 191±21 pg/ml, suggesting that pulmonary formation of PGI2 was stimulated. In the patients subjected to ECC with occluded pulmonary circulation the arterial content of 6-keto-PGF was stabilised at an elevated level (120−170 pg/ml). Following re-establishment of the pulmonary circulation the arterial concentrations of 6-keto-PGF increased markedly, to 284±50 pg/ml. It is suggested that the basal pulmonary formation of PGI2 in man is low or non-existent, and that enhanced formation of the compound in the lungs is a consequence of intervention with normal pulmonary ventilation or perfusion.  相似文献   

17.
We measured nitrous oxide (N2O), dinitrogen (N2), methane (CH4), and carbon dioxide (CO2) fluxes in horizontal and vertical flow constructed wetlands (CW) and in a riparian alder stand in southern Estonia using the closed chamber method in the period from October 2001 to November 2003. The replicates’ average values of N2O, N2, CH4 and CO2 fluxes from the riparian gray alder stand varied from −0.4 to 58 μg N2O-N m−2 h−1, 0.02–17.4 mg N2-N m−2 h−1, 0.1–265 μg CH4-C m−2 h−1 and 55–61 mg CO2-C m−2 h−1, respectively. In horizontal subsurface flow (HSSF) beds of CWs, the average N2 emission varied from 0.17 to 130 and from 0.33 to 119 mg N2-N m−2 h−1 in the vertical subsurface flow (VSSF) beds. The average N2O-N emission from the microsites above the inflow pipes of the HSSF CWs was 6.4–31 μg N2O-N m−2 h−1, whereas the outflow microsites emitted 2.4–8 μg N2O-N m−2 h−1. In VSSF beds, the same value was 35.6–44.7 μg N2O-N m−2 h−1. The average CH4 emission from the inflow and outflow microsites in the HSSF CWs differed significantly, ranging from 640 to 9715 and from 30 to 770 μg CH4-C m−2 h−1, respectively. The average CO2 emission was somewhat higher in VSSF beds (140–291 mg CO2-C m−2 h−1) and at the inflow microsites of HSSF beds (61–140 mg CO2-C m−2 h−1). The global warming potential (GWP) from N2O and CH4 was comparatively high in both types of CWs (4.8 ± 9.8 and 6.8 ± 16.2 t CO2 eq ha−1 a−1 in the HSSF CW 6.5 ± 13.0 and 5.3 ± 24.7 t CO2 eq ha−1 a−1 in the hybrid CW, respectively). The GWP of the riparian alder forest from both N2O and CH4 was relatively low (0.4 ± 1.0 and 0.1 ± 0.30 t CO2 eq ha−1 a−1, respectively), whereas the CO2-C flux was remarkable (3.5 ± 3.7 t ha−1 a−1). The global influence of CWs is not significant. Even if all global domestic wastewater were treated by wetlands, their share of the trace gas emission budget would be less than 1%.  相似文献   

18.
Uterine cervix tissue, obtained from nonpregnant fertile women undergoing hysterectomy, was mechanically chopped into 1 mm thick slices and incubated in Krebs-Ringer bicarbonate buffer containing 6-keto-PGF (0.03–10 μg/ml) and 3H-proline. After incubation of 30–120 min the incorporated radioactivity was determined and related to the protein content of each slice. 6-keto-PGF had specific and significant effects on the incorporation of 3H-proline into cervical tissue. In the follicular phase of the cycle a decreased incorporation was registered, indicating a reduced net synthesis of protein. However, increased radiolabelling was observed in the luteal phase, reflecting an augmented protein synthesis. It is suggested that 6-keto-PGF, the stable metabolite of prostacyclin (PGI2), has the ability to influence cervical protein metabolism and that this effect is steroid hormone dependent.  相似文献   

19.
Effects of 10 ppm nitrogen dioxide (NO2) exposure on the contents of prostaglandins (PGs) and thromboxane (TX) B2 in broncho-alveolar lavage (BAL) of rats were studied. In the BAL of normal rats, the amounts of PGs and TXB2 in the whole lavage were 6-keto-PGF (38.0 ± 6.4 ng) > TXB2 (11.8 ± 4.0 ng) > PGF2α (5.7 ± 1.6 ng) PGE (0.5 ± 0.3 ng). Rats were exposed to NO2 for 1, 3, 5, 7 and 14 days. The NO2 exposure decreased in the level of 6-keto-PGF by about 35% throughout the exposure. The level of TXB2 was higher in the day 5 exposure group (155%). The contents of PGF and PGE first, decreased and then transiently increased on days 3 and 5. PG 15-hydroxy-dehydrogenase activity of lung homogenate decreased correspondingly on day 3 and 5. Then the contents PGF and PGE decreased on day 7 and 14.6-keto-PGF and TXB2 are stable metabolites of PGI2, a strong bronchorelaxant and TXA2, a strong bronchoconstrictor respectively. Therefore the results suggested that the decrease in 6-keto-PGF, a major prostanoid in the BAL and the increase in TXB2 may correlate with broncho constriction by NO2 exposure.  相似文献   

20.
Uterine horns from castrated, estrogen-treated rats were superfused for 6 hours in 95% O2/5% CO2 at 37°C. The method of superfusion in which medium flows separately over the inner and outer surfaces of the horn allows prostaglandin synthesis in the myometrium and endometrium to be measured independently while their anatomical relationship is undisturbed. Prostaglandins were measured by radioimmunoassay. The myometrium formed more 6-keto-PGF than PGF whereas the opposite was true of the endometrium. Production rates of TxB2 in both tissues were relatively low. The addition of ionophore A-23187, oxytocin or phenylephrine to the superfusion medium not only increased the myometrial production rates of both 6-keto-PGF and PGF but also increased the ratio 6-keto-PGF:PGF. Neither ionophore nor phenylephrine affected the rate of prostaglandin synthesis in the endometrium whereas oxytocin caused a significant increase in the production rate of PGF. We conclude that the large amounts of 6-keto-PGF in the myometrial superfusate probably originate in both the smooth-muscle cells of the myometrium and the endothelium of the myometrial blood vessels. The differential responses to ionophore A-23187, phenylephrine and oxytocin suggest differences in the mode of their regulation of prostaglandin synthesis.  相似文献   

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