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1.
ADP (0.2−200 μN) stimulated the synthesis of prostacyclin (PGI2), as reflected by the release of 6-keto-prostaglandin F1α (6-K-PGF1α), in endothelial cells cultured from bovine orta. This effect of ADP was mimicked by ATP, whereas AMP and adenosine were completely inactive. The release of 6-K-PGF1α triggered by ADP was rapid in onset (within 5 min), transient (10 min) and followed by a period of refractoriness to a new ADP challenge. Growing and confluent cells were equally responsive to ADP. ADP stimulated the release of free arachidonic acid from the endothelial cells. ADP could be thus exert two opposite actions on platelet aggregation in vivo: a direct stimulation and an inhibition mediated by PGI2. This last action might contribute to limit thrombus formation to areas of endothelial cell damage. 相似文献
2.
A method was developed for the isolation of prostacyclin (PGI2) from whole blood in a fraction suitable for high pressure liquid chromatography (HPLC) separation of PGI2 and 6-keto-prostaglandin F1α (6-K-PGF1α). Prostacyclin was stabilized in whole blood by rapidly raising the pH to 10 with Na2CO3 and cooling the samples to 0°C. Under these conditions, 2.9% hydrolysis was observed after 20 min. Reverse phase extraction columns were used to directly extract both PGI2 and 6-K-PGF1α from the alkaline plasma with recoveries of greater than 95% using an acetonitrile/2mM Na2B4O7, pH 10,
elution solvent mixture. An additional 1.7% hydrolysis was found during the column extraction procedure. Final separation of PGI2 and 6-K-PGF1α was performed with HPLC using an alkaline solvent system. This method is capable of rapidly and efficiently extracting and separating PGI2 and 6-K-PGF1α from whole blood or plasma. It introduces less than 5% hydrolysis of PGI2, thus providing a means of applying highly sensitive 6-K-PGF1α assays to the determination of PGI2 levels in physiological samples. 相似文献
3.
J.J. Adcock L.G. Garland S. Moncada J.A. Salmon 《Prostaglandins & other lipid mediators》1978,16(2):179-187
Fragments of chopped lung from indomethacin treated guinea-pigs had an anti-aggregating effect when added to human platelet rich plasma (PRP), probably due to the production of prostacyclin (PGI2) since the effect was inhibited by 15-hydroperoxy arachidonic acid (15-HPAA, 10 μg ml−1). Both 15-HPAA (1–20 μg ml−1 min−1) and 13-hydroperoxy linoleic acid (13-HPLA, 20 μg ml−1 min−1) caused a marked enhancement of the anaphylactic release of histamine, slow-reacting substance of anaphylaxis (SRS-A) and rabbit aorta contracting substance (RCS) from guinea-pig isolated perfused lungs. This enhancement was not reversed by the concomitant infusion of either PGI2 (5 μg ml−1 min−1) or 6-oxo-prostaglandin F1α (6-oxo-PGF1α, 5 μg ml−1 min−1). Anaphylactic release of histamine and SRS-A from guinea-pig perfused lungs was not inhibited by PGI2 (10 ng - 10 μg ml−1 min−1) but was inhibited by PGE2 (5 and 10 μg ml−1 min−1). Antiserum raised to 5,6-dihydro prostacyclin (PGI1) in rabbits, which also binds PGI2, had no effect on the release of anaphylactic mediators. The fatty acid hydroperoxides may enhance mediator release either indirectly by augmenting thromboxane production or by a direct effect on sensitized cells. Further experiments to distinguish between these alternatives are described in the accompanying paper (27). 相似文献
4.
Carol Ingerman-Wojenski Melvin J. Silver J.Bryan Smith Mark Nissenbaum Albert W. Sedar 《Prostaglandins & other lipid mediators》1981,21(4):655-666
The central artery of the rabbit ear was perfused in situ and effluent fractions from the artery were assayed for 6-keto-prostaglandin F1α (6-K-PGF1α) and thromboxane B2 (TxB2), the stable metabolites of prostacyclin (PGI2) and TxA2, using specific radioimmunoassays. These metabolites of arachidonic acid (AA) were not detected in the effluent during infusion of Tyrode's solution but both metabolites were detected when small amounts of AA were infused into the artery. Examination of the arteries by scanning electron microscopy revealed that high concentrations of AA which caused a short burst of 6-K-PGF1α and TxB2 production damaged the endothelial cells while lower concentrations which stimulated continuous production did not cause damage. When a non-damaging concentration of AA was infused into an artery that the previously received a damaging concentration, PG production was greatly reduced. Pretreatment of the rabbits with 4 mg/kg acetyl-salicyclic acid (ASA) inhibited 6-K-PGF1α production by the rabbit ear artery in response to AA and 70% inhibition was still evident 18 hours after ASA. 相似文献
5.
Michael C. Madden Robert L. Vender Mitchell Friedman 《Prostaglandins & other lipid mediators》1986,31(6)
Exposure of cultured bovine pulmonary artery endothelial cells to varying levels of hypoxia (10% or 0% O2) for 4 hours resulted in a significant dose-dependent inhibition in endothelial prostacyclin synthesis (51% and 98%, at the 10% and 0% O2 levels respectively, p <0.05, compared to 21% O2 exposure values). Release of 3H-arachidonic acid from cellular pools was not altered by hypoxia. Some of the cells were incubated with arachidonic acid (20 μM for 5 min) or PGH2 (4 μM for 2 min) immediately after exposure. Endothelium exposed to 0% O2, but not to 10% O2, produced significantly less prostacyclin after addition of either arachidonic acid (25 ± 5% of 21% O2 exposure values, n=6, p <0.01) or PGH2 (31 ± 3% of 21% O2 exposure values, n=6, p <0.05). These results suggest that hypoxia inhibits cyclooxygenase at the 10% O2 level and both cyclooxygenase and prostacyclin synthetase enzymes at the 0% O2 exposure levels. Exposure of aortic endothelial cells resulted in a 44% inhibition of prostacyclin at the 0% exposure level. No significant alteration in prostacyclin production was found in pulmonary vascular smooth muscle cells exposed to hypoxia. These data suggest that the increased prostacyclin production reported in lungs exposed to hypoxia is not due to a direct effect of hypoxia on the main prostacyclin producing cells of the pulmonary circulation. 相似文献
6.
Mike A. Clark David Littlejohn Seymour Mong Stanley T. Crooke 《Prostaglandins & other lipid mediators》1986,31(1)
Incubation of the bovine endothelial cell line, CPAE, with the calcium ionophore (A23187), bradykinin (BK), leukotriene D4 (LTD4) or leukotriene C4 (LTC4) resulted in concentration dependent increases in prostacyclin release measured as 6-ketoprostaglandin F1α. The kinetics of induction of prostacyclin synthesis differed among the agents studied. Statistically significant increases in prostacyclin were observed one minute after treatment with A23187, at slightly longer times with bradykinin and after approximately three minutes with the leukotrienes. Two other leukotrienes were tested. Both leukotriene B4 and leukotriene E4 (LTE4) were inactive at con- centrations up to 10 μM. The induction of prostacyclin synthesis by LTC4 and LTD4 was inhibited by cycloheximide and actinomycin-D. The effect of BK was inhibited by cycloheximide but not by actinomycin-D. Induction by A23107 was not inhibited by either actinomycin-D or cycloheximide. The results suggest that these agents induced the increases in prostacyclin synthesis by different mechanisms. 相似文献
7.
Dedmer Schaafsma Reinoud Gosens I Sophie T Bos Herman Meurs Johan Zaagsma S Adriaan Nelemans 《Respiratory research》2005,6(1):85
Background
In addition to their proliferative and differentiating effects, several growth factors are capable of inducing a sustained airway smooth muscle (ASM) contraction. These contractile effects were previously found to be dependent on Rho-kinase and have also been associated with the production of eicosanoids. However, the precise mechanisms underlying growth factor-induced contraction are still unknown. In this study we investigated the role of contractile prostaglandins and Rho-kinase in growth factor-induced ASM contraction.Methods
Growth factor-induced contractions of guinea pig open-ring tracheal preparations were studied by isometric tension measurements. The contribution of Rho-kinase, mitogen-activated protein kinase (MAPK) and cyclooxygenase (COX) to these reponses was established, using the inhibitors Y-27632 (1 μM), U-0126 (3 μM) and indomethacin (3 μM), respectively. The Rho-kinase dependency of contractions induced by exogenously applied prostaglandin F2α (PGF2α) and prostaglandin E2 (PGE2) was also studied. In addition, the effects of the selective FP-receptor antagonist AL-8810 (10 μM) and the selective EP1-antagonist AH-6809 (10 μM) on growth factor-induced contractions were investigated, both in intact and epithelium-denuded preparations. Growth factor-induced PGF2α-and PGE2-release in the absence and presence of Y-27632, U-0126 and indomethacin, was assessed by an ELISA-assay.Results
Epidermal growth factor (EGF)-and platelet-derived growth factor (PDGF)-induced contractions of guinea pig tracheal smooth muscle preparations were dependent on Rho-kinase, MAPK and COX. Interestingly, growth factor-induced PGF2α-and PGE2-release from tracheal rings was significantly reduced by U-0126 and indomethacin, but not by Y-27632. Also, PGF2α-and PGE2-induced ASM contractions were largely dependent on Rho-kinase, in contrast to other contractile agonists like histamine. The FP-receptor antagonist AL-8810 (10 μM) significantly reduced (approximately 50 %) and the EP1-antagonist AH-6809 (10 μM) abrogated growth factor-induced contractions, similarly in intact and epithelium-denuded preparations.Conclusion
The results indicate that growth factors induce ASM contraction through contractile prostaglandins – not derived from the epithelium – which in turn rely on Rho-kinase for their contractile effects. 相似文献8.
Sodium vanadate (11 μM) amplified the PGI2 production of rat liver cells (the C-9 cell line) incubated with thrombin, platelet activating factor, lysine-vasopressin, the Ca2+-ionophore A-23187, interleukin-1ß, 12-tetradecanoylphorbol-13-acetate, teleocidin, epidermal growth factor, palytoxin, thapsigargin and colchicine but not that stimulated by exogenous arachidonic acid. Sodium vanadate (2.2 μM) also amplified PGF2α production of dog kidney cells (the MDCK cell line) incubated with norepinephrine and, at 0.4 μM, PGI2 production of bovine aorta smooth muscle cells stimulated by serotonin. Sodium vanadate (55 μM) did not affect production of PGE2 and PGF2α in rat basophil leukemia cells (the RBL-1 cell line) stimulated by the Ca2+-ionophore A-23187, but did inhibit synthesis of peptide-containing leukotrienes and 12-hydroxyeicosatetraenoic acid. When used with cultured cells at micromolar concentrations, vanadate is known to inhibit protein tyrosine-phosphate phosphatases. These results suggest that in some cells deesterification of lipids is positively regulated, at least in part, by phosphorylation of tyrosine whereas in leukocytes, lipoxygenase activities are negatively regulated, at least in part, by phosphorylation of tyrosine. 相似文献
9.
Sylvie Ben Slama Christine Bnistant Fabienne Achard Evelyne Vricel Michel Lagarde 《Prostaglandins & other lipid mediators》1995,50(2)
The cross-reactivity of the PGI3 metabolite, Δ17-6-keto-PGF1α, with antibodies against 6-keto-PGF1α for radioimmunoassays (RIA) has been investigated. Δ17-6-keto-PGF1α 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-PGF1α and Δ17-6keto-PGF1α produced were separated by RP-HPLC. Then, cross-reactivities of the commercial and purified Δ17-6-keto-PGF1α with 6-keto-PGF1α 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-PGF1α. In accordance with the cross-reactivity data, we found that RIA in media mainly measured 6-keto-PGF1α, the Δ17-6-keto-PGF1α formed being undetected at 90%. It is concluded that 6-keto-PGF1α antibodies generally used for RIA of 6-keto-PGF1α are highly specific since they can discriminate a metabolite bearing an additional double bond such as the PGI3 metabolite Δ17-6-keto-PGF1α. 相似文献
10.
Granulosa, theca and corpus luteum cells of the goat ovary were isolated and incubated separately for 6 hours, with or without various modulators. Arachidonic acid (AA, 10 ng to 100 μg/ml), the precursor for prostaglandin synthesis, produced a dose-dependent increase in progesterone (P4) and estradiol-17β (E2) productin by all the cell types. Prostaglandin synthetase inhibitors, aspirin (10−6−10−3M) and indomethacin (100 ng−1 mg/ml), produced a dose-dependent decrease in arachidonic acid-stimulated (100 μ/ml) steroid production. Prostacyclin synthetase stimulators, trapidil (1.6 μg− 1 mg/ml) and dipyridamole (10−6−10−3M), when added alone or along with AA, did not effect steroid production. Up to 100 μg/ml of U-51605 (9,11-azoprosta-5, 13-dienoic acid), a prostacyclin synthetase inhibitor, did not inhibit basal or AA-stimulated steroid production. Prostacyclin (PGl2) and its stable analog 6βPGl1(0.01–10μg/ml) produced a dose-dependent increase in P4 and E2 production in all three cell types. Increase at 1 and 10μg/ml was significant in all cases. 6-keto-PGE1 (an active metabolite of PGl2 in certain systems) produced an increase in steroid production which was significant in theca at 1μg/ml concentrations but had no significant effect on granulosa and corpus luteum cells at any dose level. 6-keto-PGf1 alpha (stable metabolite of PGl2) was without effect inthe present system. The lack of effect of PGl2 at lower concentrations was not altered by either differentiation of the cells with FSH and testosterone or addition of steroid precursors, testosterone and pregnenolene. The present results indicate that AA- stimualted steroid production in the goat ovarian cell type is mediated by prostaglandins other than PGl2 though PGl2 itself can positively modulate the steroid production. 相似文献
11.
M.D. Mitchell J.G. Bibby B.R. Hicks A.C. Turnbull 《Prostaglandins & other lipid mediators》1978,16(6):931-937
Human amnion, chorion, decidua and placenta produced 6-oxo-PGF1α when superfused
. Furthermore amnion, an avascular tissue, produced more 6-oxo-PGF1α after labour than all other tissues investigated and its production of 6-oxo-PGF1α was significantly greater after labour than before the onset of labour. These findings suggest that prostacyclin production by foetal membranes may have a role in the mechanisms controlling human parturition. Moreover, this is the first evidence for the production of prostacyclin by an avascular tissue. 相似文献
12.
Eugen H. O'Keefe Edward C.K. Liu Roland Greenberg Martin L. Ogletree 《Prostaglandins & other lipid mediators》1985,29(5):785-797
The TxA2 synthetase inhibitor, dazoxiben, and the TxA2 antagonist, ±SQ 29, 548, were examined for effects on release and vasoactivity of TxA2 and prostacyclin. Isolated perfused guinea pig lungs were used as the enzyme source from which TxA2 and prostacyclin were released in response to injections of arachidonic acid or bradykinin. Both dazoxiben and ±SQ 29, 548 inhibited contraction of the superfused rat aorta and bovine coronary artery after arachidonic acid injection through the lung. ±SQ 29, 548 abolished contractions of the rat aorta, but significant aorta contracting activity persisted during dazoxiben treatment. Dazoxiben significantly inhibited arachidonate-induced release of TxA2 (immunoreactive TxB2)iinto the superfusate, but TxA2 release was significantly potentiated by ±SQ 29, 548. Thus, in the presence of enhanced TxA2 concentrations, ±SQ 29, 548 effectively antagonized the vasospastic effect of TxA2. Dazoxiben diverted a significantly greater amount of arachidonic acid into prostacyclin synthesis (immunoreactive 6-keto-PGF1α), changing original coronary vasoconstriction into relaxation. ±SQ 29, 548 did not significantly modify lung prostacyclin synthesis. Moreover, with ±SQ 29, 548, the absence of TxA2-mediated coronary contraction unmasked active relaxation of the superfused bovine coronary artery, coincident with thromboxane and prostacyclin release. Dazoxiben consistently inhibited TxA2 synthesis and enhanced prostacyclin synthesis. ±SQ 29, 548 augmented TxB2 release in response to arachidonate, but not bradykinin, and did not significantly alter 6-keto-PGF1α release in response to either arachidonate or bradykinin. In terms of vasoactivity measured
, ±SQ 29, 548 and dazoxiben produced similar anti-vasospastic effects, although this was accomplished by completely different mechanisms. 相似文献
13.
R.D. Nolan G.J. Dusting J. Jakubowski T.J. Martin 《Prostaglandins & other lipid mediators》1982,24(6):887-902
Cyclo-oxygenase products of arachidonic acid metabolism formed by the pericardium and epicardial surface of dog heart were identified and quantitated by radioimmunoassay after separation by high-pressure liquid chromatography. Pieces of pariental pericardium, of dog, ox and rat, when incubated
produced mainly 6-keto-PGF1α, with lesser amounts of PGE2, PGF2α and thromboxane B2. Biosynthesis of all prostanoids increased during incubation of the pariental pericardium of each species with arachidonic acid, but 6-keto-PGF1α was still the major metabolite. When slices of dog heart were incubated with arachidonic acid (1 μg/ml) the rates of 6-keto-PGF1α formation by the pariental pericardium was much greater than that of the myocardium and endocardium. Epicardial slices appeared to be intermediate in 6-keto-PGF1α formation. The hearts of anesthetized dogs were also irrigated
with Krebs' solution, and during the first 5 min of epicardial irrigation the pericardial fluid leaving the heart again contained high levels of 6-keto-PGF1α, with lesser amounts of the other prostanoids. Addition of arachidonic acid (3 μg/ml) to the irrigating fluid caused an increase in all measured prostanoid levels, although 6-keto-PGF1α remained the predominant metabolite. In contrast, intravenous infusion of isoproterenol selectively increased the release of 6-keto-PGF1α from the irrigated heart. It is concluded that the pericardium and epicardium continuously release prostacyclin into the pericardial fluid, and that the increased release of this substance observed when cardiac workload increases derives mainly from these membranous sources. This raises the interesting possibility that pericardial prostacyclin might influence coronary vascular tone and chemoreflexes which arise from the epicardium during myocardial ischemia. 相似文献
14.
The release of prostacyclin from chopped myometrial fractions of 18–20 day pregnant rats was assayed by inhibition of ADP-induced aggregation of citrated rabbit platelet-rich plasma. Preincubation of myometrial tissue with oxytocin 10 mU/ml increased prostacyclin generation from 2.25 ± 0.48 (control) to 3.75 ± 0.73 ng/mg over 15 minutes. Bradykinin 20 μg/ml also caused a significant increase in myometrial prostacyclin output from 2.26 ± 0.19 to 4.26 ± 0.64 ng/mg. PGF2α 1 μg/ml did not increase prostacyclin release significantly. Pretreatment of myometrial tissue with the phospholipase inhibitor mepacrine significantly reduced the peptide-stimulated release of prostacyclin. The results suggest that prostacyclin production may play an important role in modulating the actions of oxytocin and bradykinin in the pregnant rat myometrium. 相似文献
15.
Catherine Delarue Isabelle Perroteau Isabelle Lirhmann Pierre Netchitailo Franoise Homo-Delarche Hubert Vaudry 《Prostaglandins & other lipid mediators》1986,31(1)
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-PGF1α 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-PGF1α, the stable metabolite of PGI2. The increase of 6-keto-PGF1α preceded the stimulation of corticosterone and aldosterone secretions. In contrast, the administration of ACTH did not modify the release of 6-keto-PGF1α. 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
16.
The vascular actions of several prostanoids and arachidonate lipoxygenase products were investigated on the gastric circulation of rat and rabbit
perfused with Kreb's solution. Under resting conditions, prostacyclin and PGE2 produced small decreases in perfusion pressure with prostacyclin being the more potent. During vasoconstriction induced by infusion of noradrenaline, vasopressin or angiotensin II, prostacyclin was 20–40 times as active as PGE2 as a gastric vasodilator in rat or rabbit stomach. PGF2α was a less potent vasoconstrictor than noradrenaline, while the epoxy-methano endoperoxide analogue produced a long-lasting vasoconstriction. The putative metabolite, 6-oxo-PGE1 was less active than prostacyclin as a vasodilator, having comparable activity to PGE1, whereas 6-oxo-PGF1α had very little activity. The endoperoxide, PGH2 reduced perfusion pressure, this effect being inhibited by concurrent infusion of 15-HPETE. The vasodilation induced by arachidonic acid was likewise reduced by 15-HPETE, and abolished by indomethacin infusion. The arachidonate lipoxygenase hydroperoxides were vasodilator in the gastric circulation, the rank order of potency being 12-HPETE > 11-HPETE > 5-HPETE > 15-HPETE in both rat and rabbit stomach. It is possible that such vasoactive lipoxygenase products, may play modulator roles in the gastric mucosa. 相似文献
17.
C.S. Holladay R.M. Wright B.L. Spangelo 《Prostaglandins, leukotrienes, and essential fatty acids》1993,49(6)
Interleukin-6 (IL-6) is a cytokine involved in the differentiation of B-cells to antibody secreting plasma cells, the activation of T-cells, and the stimulation of hepatocyte production of acute phase proteins. Because of the pro-inflammatory effects of this cytokine, we investigated the ability of the fatty acid arachidonic acid (AA) to regulate the release of IL-6 from rat resident peritoneal macrophages (Mø) in vitro. AA (0.5–16 μM) stimulated IL-6 release during a 4 h incubation period in a biphasic manner, with 4 μM AA generating a peak of IL-6 release (3-5-fold). AA (0.5–16 μM) also induced an increasing release of the AA metabolite thromboxane B2 (TXB2). The AA-induced release of IL-6 occurred within 1–2 h of incubation, whereas TXB2 concentrations were elevated within 5 min of AA treatment. The TX synthetase inhibitor CGS 12970 (4.0 μM and 40.0 μM) effectively blocked the generation of TXB2, but increased prostacyclin (PGI2) generation and potentiated the release of IL-6. In addition, PGI2, as well as the PGI2 agonists iloprost and cicaprost, stimulated IL-6 release from Mø by greater than 5-fold over vehicle-treated basal levels. These data suggest that PGI2 (but not TXA2) is involved in AA-induced IL-6 release from peritoneal Mø. 相似文献
18.
An enzyme-linked immunosorbent assay for 6-keto prostaglandin F1α, a stable metabolite of prostacyclin, has been developed. The assay allows quantitation of 6-keto PGF1α in the range 1–200 pg/0.1 ml and shows very low cross reactivity to nine other prostaglandins. Dose dependent stimulation by thrombin of 6-keto PGF1α formation in human endothelial cells in culture has been used to verify the assay. Quantitation by the enzyme linked immunosorbent assay agrees closely with determination by radioimmunoassay. 相似文献
19.
A nitric oxide synthesis inhibitor decreased prostaglandin production in rat mesenteric vasculature 总被引:1,自引:0,他引:1
Masayoshi Soma Yoichi Izumi Yoshiyasu Watanabe Katsuo Kanmatsuse 《Prostaglandins & other lipid mediators》1996,51(3):225-232
Endothelial cells synthesize and release nitric oxide (NO) and prostacyclin (PGI2) which are involved in the regulation o f vascular tone and blood pressure. Our objective was to evaluate the effects of inhibiting NO synthesis on vascular prostaglandin (PG) and cyclic nucleotide production, as well as the pressor response to norepinephrine (NE). Isolated mesenteric arterial beds were perfused with Krebs-Henseleit solution containing 100 μM NG-monomethyl-L-arginine (L-NMMA), 100 μM L-arginine (LA), or vehicle. After a 30 min equilibration 0.1, 0.5, 1, or 5 μM NE was infused into the superior mesenteric artery and the perfusion pressure was monitored. The basal perfusion pressure did not differ significantly between groups. The pressure-response curve was shifted to the right in the L-NMMA group vs. the LA and control groups. Perfusion was similarly performed with a Krebs-Henseleit solution containing 100 μM L-NMMA, LA, D-arginine, or vehicle. Perfusates were collected before and after NE infusion for the measurement of PGE2, 6-keto-PGF1α, TxB2, cAMP, and cGMP. In the L-NMMA group the release of PGE2 and 6-keto-PGF1α was decreased, and the release of cGMP was prevented. Production of cAMP did not differ between the four groups before NE infusion, and NE increased cAMP release in the L-NMMA group and controls. The results indicate that inhibition of NO synthesis by L-NMMA enhanced the pressor response to NE, possibly mediated by the decreased cGMP and PGI2 production in resistance vessels. 相似文献
20.
The effects of lanthanum(La) on contractions induced by prostaglandin F2α(PGF2α) or isotonic K+ were investigated in the isolated stomach muscle of guinea-pig.Low concentrations of La(0.1–1 μM) inhibited the contraction to PGF2α 1 μM in a dose-dependent manner, without affecting the tonic contraction to isotonic K+.0.1 and 1 μM La shifted the dose-response curve for PGF2α(0.001 – 1 μM) to the right and reduced the maximum response.The IC50 of La against PGF2α and K+ were 0.6 μM and 30 μM, respectively.These results support the suggestion that PGF2α -induced contraction in the stomach muscle depends mainly on the intracellular release of sequestered Ca, which would be depleted or immobilized by La. 相似文献