共查询到20条相似文献,搜索用时 31 毫秒
1.
H.L. Lippton B.M. Chapnick A.L. Hyman P.J. Kadowitz 《Prostaglandins & other lipid mediators》1980,19(2):299-310
The effects of 6-keto-PGE1 on vascular resistance and vascular responses to sympathetic nerve stimulation and vasoconstrictor hormones were investigated in the feline mesenteric vascular bed. Infusions of 6-keto-PGE1 into the superior mesenteric artery dilated the mesenteric vascular bed and markedly inhibited vasoconstrictor responses to sympathetic nerve stimulation, norepinephrine and angiotensin II. The effects of 6-keto-PGE1 and PGE1 on vascular resistance and vasoconstrictor responses were quite similar and both substances inhibited responses to nerve stimulation and pressor hormones in a reversible manner. Responses to nerve stimulation, norepinephrine and angiotensin II were inhibited to a similar extent during infusion of 6-keto-PGE1 and PGE1. Results of these studies suggest that 6-keto-PGE1, a newly identified prostaglandin metabolite, and PGE1 possess the ability to inhibit the vasconstrictor effects of sympathetic nerve stimulation and pressor hormones by a nonspecific action on vascular smooth muscle in the feline small intestine. 相似文献
2.
Yutaka Suzuki Yoshiteru Harada Akinori Ueno Makoto Katori Haruya Okabe 《Prostaglandins & other lipid mediators》1986,32(3)
Filling of the gastric lumen of rats with 1.0 M NaCl solution (5 ml) for 10 min under urethane anesthesia caused an increase in the gastric fluid concentrations of prostaglandin (PG) E2, 13, 14-dihydro-15-keto-PGE2 and 6-keto-PGF1α as determined by radioimmunoassay. PGE2 was the major PG generated. The levels of PGE2 in the gastric fluid were increased dose-dependently after filling the lumen with 0.3, 0.5, 0.7 or 1.0 M NaCl solutions. The pH of the gastric fluid increased similarly after 0.5 to 1.0 M NaCl solutions. Indomethacin (10 mg/kg, i.p.) suppressed the PGE2 increase caused by 1.0 M NaCl solution, but did not prevent the increase of the pH of the gastric fluid induced by intragastric 1.0 M NaCl. Infusion of tetragastrin (62.5 μg/kg/hr, i.v., for 10 min) caused a marked increase of acid secretion without modifying intragastic concentration of PGE2. The acid secretion due to tetragastrin was completely inhibited after intragastric administration of 1.0 M NaCl solution, while indomethacin restored the tetragastrin-induced acid secretion, with prevention of a rise of intragastric PGE2 levels. These observations suggest that 1.0 M NaCl solutions suppress basal intragastric acid through a mechanism which is independent of prostaglandins. In contrast, the suppression of tetragastrin-induced acid secretion by intragastric 1.0 M NaCl solution appears to be mediated through a release of prostaglandins 相似文献
3.
《Prostaglandins and medicine》1980,4(4):227-237
Cyclooxygenase products of arachidonic acid metabolism in the plasma of normal rabbits and animals bearing the VX2 carcinoma were separated by high performance liquid chromatography and the effluent fractions assayed by serologic methods. The products measured were 6-keto-PGFlα, thromboxane B2, PGE2, PGF2α, 13,14-dihydro-PGE2, 13,14-dihydro-15-keto-PGE2, 15-keto-PGE2, and 13,4-dihydro-15-keto-PGF2α. In hypercalcemic, tumor-bearing rabbts, the plasma concentrations o 13,14-dihydro-15-keto-PGE2 and 13,14-dihydro-15-keto-PGF2α were markedly elevated (in the range of 0.5 to 16 ng/ml). Previously unmeasured 6-keto-PGF1α, thromboxape B2, 13,14-dihydro-PGE2 and 15-keto-PGE2 were not found in high concentrations in the plasma of tumor-bearing rabbits. These results add further support to our conclusion that the VX2 tumor produces hypercalcemia in the host by a mechanism which utilizes PGE2, rather than a subsequent metabolite of this prostaglandin, as the mediator between the neoplasm and bone. 相似文献
4.
F. Coceani E. Bodach E.P. White P.M. Olley 《Prostaglandins & other lipid mediators》1980,19(1):109-113
6-Keto-PGE1 is nearly as potent as PGE2 in relaxing the ductus arteriosus of fetal lambs. This finding raises the possibility that 6-keto-PGE1, if occuring naturally as a by-product of PGI2 transformations, may contribute to prenatal patency of the vessel. 相似文献
5.
Fred C. Falkner 《Prostaglandins & other lipid mediators》1979,18(5):779-786
After intratracheal administration to rats, the bronchodilator N-acetyl PGE2 carboxamide was converted rapidly to PGE2 and 13,14-dihydro-15-keto-PGE2, the major plasma metabolite. Oxidation of the N-acetyl carboxamide by prostaglandin dehydrogenase and hydrolysis of the imide bond were demonstrated in vitro. 相似文献
6.
Nimodipine, a new calcium channel blocker, was found to prolong survival in a severely lethal form of traumatic shock in rats. Nimodipine, at infusion rates of 50 μg/kg/h also significantly limited the increase in circulating myocardial depressant factor (MDF) without significantly preventing the accumulation of the lysosomal protease, cathepsin D in the blood. Lower infusion rates were ineffective. Nimodipine did not stabilize lysosomal membranes directly in liver lysosomal suspensions, but was effective in preventing proteolysis in pancreatic homogenates. Nimodipine potentially prevents MDF formation by inhibiting proteases and probably by splanchnic vasodilation. Calcium channel blockers may be useful agents in the therapeutics of traumatic shock if given soon after the onset of the trauma. 相似文献
7.
Accumulation of Cyclooxygenase Products of Arachidonic Acid Metabolism in Gerbil Brain During Reperfusion After Bilateral Common Carotid Artery Occlusion 总被引:22,自引:7,他引:15
: Several of the cyclooxygenase products of arachidonic acid were measured in the cerebral hemispheres of gerbils subjected to transient interruption of the cerebral circulation. The levels of PGD2, PGF2α, PGE2, TXB2, 13,14-H2-15-keto-PGE2, and the stable nonenzymic product of prostacyclin, 6-keto-PGF1α, were not altered at the end of a 5-min period of ischemia. However, the onset of reperfusion was accompanied by a rapid accumulation of these products. Levels were highest during the initial period of reperfusion, then decreased to approach control levels after 120 min. PGD2, PGF2α, and PGE2 were the predominant metabolites detected. This postischemic accumulation of arachidonic acid metabolites could be blocked by prior administration of inhibitors of cyclooxygenase activity. 相似文献
8.
PGE2 can vasoconstrict or vasolidate the isolated Krebs-perfused rat kidney depending on the tone of the renal vasculature. Thus, it is weakly constrictor (threshold 5–10 ng bolus dose) in the perfused kidney whose perfusion pressure is 47 ± 2 SD mmHg (n = 6), but becomes a vasodilator (threshold ~ 10 pg) in the kidney whose perfusion pressure has been raised to 73 ± 6 SD mmHg (n = 6) or 121 ± 8 SD mmHg (n = 6) through constant infusion of Vasopressin (0.1 and 0.25 mU/ml respectively). PGE1 was equally effective as PGE2 while other PGs, I2, I1, and 6-keto E1, were less effective in opposing vasoconstriction. PGF2α was inactive up to a dose of 10 ng. 相似文献
9.
R.L. Hbert C. Lamoureux P. Sirois P. Braquet G.E. Plante 《Prostaglandins & other lipid mediators》1987,33(2)
Recent experiments indicate that prostaglandin E2 potentiates the vasodilatory properties of leukotrienes in the skin microcirculation. The present experiments were undertaken to study the effect of leukotriene D4 and prostaglandin E2 on renal hemodynamics and urinary electrolytes in the dog. Experiments were performed in three groups of anesthetized Mongrel dogs: the first group was studied under hydropenia, whereas the two remaining groups were studied during water diuresis with (Group 3) or without indomethacin (Group 2). LTD4 (100ng/min) and PGE2 (3ug/min) were infused in the left renal artery to minimize systemic effects of these compounds. LTD4 alone failed to influence urinary sodium excretion in all 3 groups. In Group 1, urinary sodium increased from 77 ± 6 to 393 ± 74uEq/min during PGE2, and further increased to 511 ± 52uEq/min during LTD4 + PGE2. No change occured in the contralateral right kidney. In this group, glomerular filtration as well as renal plasma flow were not statistically influenced. In Group 2, the same phenomenon was observed for urinary sodium. The combined infusion of LTD4 + PGE2 increased urinary sodium without significant changes in glomerular filtration and renal plasma flow. Finally, in Group 3, indomethacin was shown to reduce the natriuretic effects of LTD4 and PGE2: during PGE2 alone, urinary sodium increased from 90 ± 14 to 260 ± 66uEq/min, and only rose from 80 ± 10 to 175 ± 19uEq/min during the combined infusion of LTD4 and PGE2. In groups 2 and 3, free water clearance was utilized as an index of sodium chloride reabsorption in the thick ascending limb: this parameter increased from 2.35 ± 0.25 to 4.70 ± 0.30ml/min, while urinary volume was increasing from 3.55 ± 0.25 to 10.05 ± 0.65ml/min, during LTD4 + PGE2. Indomethacin, administered in Group 3, (3mg/kg/hr) again abolished the effect of combined PGE2 + LTD4. These results indicate a potentiating effect of leukotriene D4 on the PGE2-induced natriuresis in the anesthetized dog. These phenomena occured in the absence of significant changes in renal hemodynamics, therefore suggesting a direct tubular effect of these arachidonic acid metabolites. Finally, the water diuresis experiments suggest a proximal site of action of PGE2 and LTD4. 相似文献
10.
Infusion of prostaglandin E1 (PGE1) into the renal artery of anesthetized dogs (1.03 μg/min) caused increases in urine flow rate (V), renal plasma flow (RPF) and renin secretion rate without any change in mean arterial blood pressure (MABP), whereas infusion of prostaglandin F2α (PGF2α), (1.03 μg/min) caused no consistent change in V, RPF, or renin secretion rate. Infusion of prostaglandin E2 (PGE2) (1.03 μg/min) into the renal artery of “non-filtering” kidneys caused renin secretion rate to rise from 567.7 ± 152.0 U/min(M ± SEM) during control periods to 1373.6 ± 358.5 U/min after 60 minutes of infusion of PGE2 (P < 0.01), without significant change in MABP (P > 0.1). The data suggest that PGE1 and PGE2 play a role in the control of renin secretion. The data further suggest that PGE may control renin secretion through a direct effect on renin-secreting granular cells. 相似文献
11.
We studied the effects of two structurally unrelated inhibitors of the fatty acid cyclooxygenase and of alpha and beta adrenergic blockade on the elevated plasma levels of 13,14-dihydro-15-keto-prostaglandin (PG)E2, 6-keto-PGF1α and thromboxane(TX)B2, the stable derivatives of PGE2, PGI2 (prostacyclin) and TXA2, respectively, in rats with streptozotocin-induced diabetic ketoacidosis (DKA). Meclofenamic acid and indomethacin each produced a significant decrease in the elevated plasma levels of 13,14-dihydro-15-keto-PGE2, 6-keto-PGF1α and TXB2. Phentolamine significantly reduced the plasma level of TXB2 but had no effect on the elevated circulating levels of glucose, free fatty acids, total ketones, 13,14,-dihydro-15-keto-PGE2 or 6-keto-PGF1α. Propranolol significantly reduced the elevated circulating levels of glucose, free fatty acids and total ketones but had no effect on the levels of the three prostaglandin derivatives. The ability of meclofenamic acid and indomethacin to reduce the plasma levels of 13,14-dihydro-15-keto-PGE2, 6-keto-PGF1α and TXB2 confirms that the plasma levels of these three derivatives are elevated in rats with DKA. Since abnormalities in the production of PGI2 and perhaps other cyclooxygenase derivatives may contribute to the pathogenesis of certain important hemodynamic and gastrointestinal features of DKA, cyclooxygenase inhibitors may play a role in the management of selected patients with this disorder. Alpha adrenergic activity is essential for the maintenance of the elevated plasma TXB2 level in rats with DKA. The fall in the plasma TXB2 level during alpha adrenergic blockade appears to reflect inhibition of platelet aggregation and platelet TXA2 production, but other sources of the elevated plasma TXB2 level in DKA are not excluded. Beta adrenergic activity contributes to the maintenance of elevated circulating levels of glucose, free fatty acids and total ketones in experimental DKA but not to the elevated plasma levels of the prostaglandin derivatives. 相似文献
12.
J. Evans R. Zamboni D. Nathaniel C. Leveill A. W. Ford-Hutchinson 《Prostaglandins & other lipid mediators》1985,30(6):981-988
The effect of micropuncture of the renal papilla through an intact ureter on urinary concetrating ability of rats was examined. Micropuncture of the renal papilla caused a fall in urine osmolality in the punctured kidney from 1718 ± 106 to 1035 ± 79 mosmol/kg·H2O. In order to investigate the role of renal prostaglandins in this process, PGE2 excretion was measured and found to increase from 63.4 ± 14.0 to 205.5 ± 57.1 pg/min. Urine osmolality and PGE2 excretion from the contralateral kidney were not significantly altered. In animals given meclofenamate (2 mg/kg·hr), renal PGE2 excretion was reduced to 22.3 ± 5.1 pg/min prior to micropuncture and it remained low at 8.9 ± 1.8pg/min after papillary micropuncture. Meclofenamate also blocked the fall in urine osmolality caused by micropuncture of the renal papilla, with urine osmolality averaging 1940 ± 122 before and 1782 ± 96 mosmol/kg·H2O after the micropuncture. These results indicated that papillary micropuncture through an intact ureter increased renal PGE2 excretion and that a rise in renal production of PGE2 or some other prostanoid is associated with a fall in urine concentrating ability. 相似文献
13.
Experiments were performed in rats to study the effect of infusion of PGI2, PGE2, and PGF2α on tubuloglomerular feedback responses (i.e. the change of SNGFR in response to a change of loop of Henle flow rate) in the presence and absence of simultaneous inhibition of endogenous PG synthesis with indomethacin. Infusion of PGI2 or PGE2 at rates that did not alter arterial blood pressure did not significantly modify the magnitude of feedback responses (PGI2) 8.5 μg/hr, PGE2 85 μg/hr). Some inhibition of feedback responses was seen when PGI2 and PGE2 were administered at higher rates were associated with a reduction of blood pressure (PGI2 20 μg/hr, PGE2 200 μg/hr). PGI2 (8.5 μg/hr) and PGE2 (85 μg/hr) largely prevented feedback inhibition induced by indomethacin. When given subsequent to indomethacin PGI2 and PGE2 restored feedback responsiveness almost to normal. In contrast, PGF2α did not influence feedback inhibition caused by indomethacin. Infusion of PGI2 induced partial restoration of feedback responses in DOCA-salt treated animals in which the feedback system is virtually completely inactive. Our results indicate that availability of PGI2 or PGE2 is necessary for the normal operation of the tubuloglomerular feedback mechanism for control of nephron filtration rate. 相似文献
14.
Sephadex LH 20 columns have been investigated for the separation of initial prostaglandin metabolites. Solvent systems are described for the separation of the free acids of 15-keto-dihydro-PGE1, 15-keto-PGE1, PGE1, and PGF1α. Further, one of the solvent systems is described for the separation of pulmonary metabolites of PGE1 and PGF1α, and anotehr one for separation of dihydro-PGE1 and PGE1. 相似文献
15.
Suzanne Desjardins-Giasson Jolanta Gutkowska Raul Garcia Jacques Genest 《Prostaglandins & other lipid mediators》1982,24(1):105-114
Prostaglandin E2 (PGE2) and 6 keto-PGF1α, the stable metabolite of prostacyclin (PGI2), have been measured in the effluent of perfused rat mesenteric arteries by the use of a sensitive and specific radioimmunoadday (RIA) method. The PGE2 and 6-keto-PGF1α were continuousyl released by the unstimulated mesenteric artery over a period of 145 min. After 100 min of perfusion the release of PGE2 and 6-keto-PGF1α was 4.5 ± 8.4 pg/min and 254 ± 75 pg.min respectively, which is in accord with the general belief that PGI2 is the major PG synthesized by arterial tissue. Angiotensin II (AII) 5 ng/ml) induced an increased of PGE2 and 6-keto-PGF1α release without changing the perfusion pressure. The effect of norepinephrine (NE) injections on release of PGs depended on the duration of the stabilization period. The changes of perfusion pressure induced by NE were not related to changes in release of PGs. Thus, it seems that the increase of PG release induced by AII and NE was due to a direct effect of the drugs on the vascular wall. This may represent an important modulating mechanism in the regulation of vascular tone. 相似文献
16.
A method is described for measurement of the cyclooxygenase products, thromboxane,prostacyclin, and prostaglandins (PG), and several prostaglandin metabolites. The procedure involves separation of the compounds by high-pressure liquid chromatography combined with identification and estimation by serologic analysis. These combined procedures have been used to identify and estimate five such products, PGE2, PGE1 PGF2α, PGF1α, and 6-keto-PGF1α, in the culture fluids of dog kidney cells stimulated by a tumor-promoting phorbol diester. The prostaglandin metabolites, 13,14-dihydro-15-keto-PGE2, 13,14-dihydro-15-keto-PF22α, 13,14-dihydro-PGE2, and 13,14-dihydro-PGF2α, were not found in these culture fluids. 相似文献
17.
A.L. Gimeno M. Chaud A. Bonacossa A.M. Franchi M.F. Gimeno 《Prostaglandins & other lipid mediators》1983,26(4):663-676
Dose-response curves for several prostaglandins (PGI2; PGD2; PGF2 and PGE2); BaCl2 or prostaglandin metabolites (15-keto-PGF2α; 13, 14-diOH-15-keto-PGF2α; 6-keto-PGF1α and 6-keto-PGE1 in quiescent (indomethacin-treated) uterine strips from ovariectomized rats, were constructed. All PGs tested as well as BaCl2, triggered at different concentrations, evident phasic contractions. Within the range of concentrations tested the portion of the curves for the metabolites of PGF2α was shifted to the right of that for PGF2α itself; the curve for 6-keto-PGF1α was displaced to the right of the curve for PGI2 and that for 6-keto-PGE1 to the left.It was also demonstrated that the uterine motility elicited by 10−5 M PGF2α and its metabolites was long lasting (more than 3 hours) and so it was the activity evoked by PGI2; 6-keto-PGF1α and BaCl2, but not the contractions following 6-keto-PGE1, which disappeared much earlier. The contractile tension after PGF2α; 15-keto-PGF2α; 13, 14-diOH-15-keto-PGF2α and PGI2, increased as time progressed whilst that evoked by 6-keto-PGF2α or BaCl2 fluctuated during the same period around more constant levels.The surprising sustained and gradually increasing contractile activity after a single dose of an unstable prostaglandin such as PGI2, on the isolated rat uterus rendered quiescent by indomethacin, is discussed in terms of an effect associated to its transformation into more stable metabolites (6-keto-PGF1α, or another not tested) or as a consequence of a factor which might protects prostacyclin from inactivation. 相似文献
18.
Charles W. Weems Thomas P. Huecksteadt Herianto Sjahli Patrick Lavelle 《Prostaglandins & other lipid mediators》1979,17(6):891-901
Effects of PGE1 or PGE2 on luteal function were studied in 163 pseudopregnant rats. PGE1 (10, 100, or 300μg) given intrauterine every 6 hr did not shorten pseudopregnancy (P < 0.05), however, the same doses of PGE2 given intrauterine every 6 hr advanced luteolysis (P < 0.05). PGE1 (100 or 300μg) given every 4 hr intramuscular maintained levels of progesterone in peripheral blood above controls (P < 0.05) while 100 or 300μg of PGE2 hastened the decline in progesterone (P < 0.05). The antiluteolytic effect of PGE1 was not via an inhibition of PGF secretion (P < 0.05) by the uterus or by induction of ovulation in treated animals. Moreover, PGE1 (100, 200, or 500μg) given intramuscular every 4 hr from day 4 of pseudopregnancy until the next proestrus delayed luteal regression around 3 days (P < 0.05). PGE2 at doses of 100, 200, or 500μg every 4 hr given intramuscular consistently shortened pseudopregnancy (P < 0.05). Lower doses were without effect (P < 0.05). Based on the above data it is concluded that PGE2 is consistently luteolytic whereas PGE1 is not luteolytic in pseudopregnant rats and that PGE1 may be an antiluteolysin. 相似文献
19.
Patrick Y-K Wong Kafait U. Malik Dominic M. Desiderio John C. McGiff Frank F. Sun 《Biochemical and biophysical research communications》1980,93(2):486-494
Metabolism of [9-3H]-PGI2 was studied in the isolated Tyrode's perfused rabbit liver. Five products, four radioactive and one non-radioactive, were identified in the perfusate: 19-hydroxy-6-keto-PGF1α, 6-keto-PGF1α, dinor-6-keto-PGF1α, pentanor PGF1α and a 6-keto-PGE1-like substance. The first two, 19-hydroxy-6-keto-PGF1α and 6-keto-PGF1α, represented 5% and 45% respectively, of the total radioactivity; the last two accounted for 39%. The presence of dinor and pentanor derivatives of 6-keto-PGF1α indicated that β -oxidation and oxidative-decarboxylation occurs in the liver as the major metabolic pathway of PGI2. One non-radioactive metabolite which co-migrated with authentic 6-keto-PGE1 was found to inhibit platelet aggregation, having a potency similar to authentic 6-keto-PGE1, and its effect can be eliminated by boiling and by alkali treatment. This metabolite, having similar Rf value on TLC and biological behavior as 6-keto-PGE1, may arise from oxidation of 6-keto-PGF1α via the 9-hydroxyprostaglandin dehydrogenase pathway, as suggested by recovery of tritiated water in the aqueous phase of the perfusate. This material, a potent inhibitor of platelet aggregation, may arise from PGI2 or its hydrolysis product, 6-keto-PGF1α. 相似文献
20.
O.V. Miller J.W. Aiken R.J. Shebuski R.R. Gorman 《Prostaglandins & other lipid mediators》1980,20(2):391-400
A direct comparison of the relative potencies of the two anti-aggregatory prostaglandins PGI2 and 6-keto-PGE1 showed PGI2 was at least 20 times more potent than 6-keto-PGE1 when tested against ADP-induced human platelet aggregation. This marked difference in potency was even more evident when the ability of PGI2 and 6-keto-PGE1 to stimulate platelet cyclic AMP levels was determined. When cyclic AMP levels were measured direct comparisons were difficult because the respective dose response curves were not parallel, but 10 ng of PGI2 was equivalent to 300 ng of 6-keto-PGE1.PGI2 was also more potent (10–20 times) than 6-keto-PGE1 as a disaggregatory agent, and the disaggregatory activity of both prostaglandins was enhanced by the phosphodiesterase inhibitor 1-methyl-3-isobutylmethylxanthine.PGI2 was also more active than 6-keto-PGE1 as an inhibitor of thrombus formation in dog coronary arteries in vivo. In vivo, 6-keto-PGE1 was at least 10 times less potent than PGI2, the exact difference could not be determined because 6-keto-PGE1 caused significant falls in blood pressure before anti-platelet activity could be detected.PGI2 is an intrinsically more potent anti-aggregatory molecule than 6-keto-PGE1, but these data do not rule out the possibility that some of the activities attributed to PGI2 could be the result of the conversion of PGI2 and/or 6-keto-PGF1α to 6-keto-PGE1. 相似文献