共查询到20条相似文献,搜索用时 15 毫秒
1.
To test the hypothesis that abnormal prostaglandin reactivity may be a characteristic of essential hypertension, cardiovascular responses to prostaglandin F2α (PGF2α) were measured in young spontaneously hypertensive (SHR) and Wistar normotensive rats (NR). PGF2α(1 sec injection; 50 l/100 g.; .05, .5, 5, 50 g salt/kg) was injected retrograde into the femoral artery. Maximum changes were measured with respect to: 1) four different diameter categories of cremaster muscle arterioles, 2) mean arterial pressure (MAP), 3) pulse pressure (PP) and 4) heart rate. PGF2α at 5 and 50 g/kg significantly increased NR and SHR blood pressure. SHR MAP increased significantly more than NR MAP with the 50 g dose (P <. 001). PGF2α increased NR PP at the 50 g/kg dose and increased SHR PP at the .5, 5 and 50 g/kg dose. SHR PP response was significantly greater than that of the NR with the .5, 5 and 50 g/kg dose (P < .05, .01, .001 respectively). The mean SHR arteriolar constriction was greater than that of NR with the 50 g dose. The only change in heart rate was a 3% decrease from control in both NR and SHR during the pressor response to 50 g/kg. These results show an increased cardiovascular reactivity to PGF2α in SHR and may further suggest prostaglandin involvement in hypertensive disease. 相似文献
2.
Martin A. Wasserman 《Prostaglandins & other lipid mediators》1975,9(6):959-973
The airway and lung dynamics of prostaglandin F2α (PGF2α) and three of its metabolites were examined in the spontaneously-ventilated, pentobarbital anesthetized dog. Changes in expiratory flow rate, tidal volume, respiration rate, lung resistance and dynamic lung compliance were evaluated and compared quantitatively. In a dose range of 0.3–3.0 μg/kg i.v., PGF2α and its 13,14-dihydro metabolite were found to be exceptionally potent agents. This metabolite was approximately twice as potent as PGF2α on most parameters studied. Two other metabolites, 15-keto-PGF2α and 15-keto-13,14-dihydro-PGF2α, were only slightly effective, even in a dose range of 1.0–30.0 μg/kg i.v. These latter two metabolites produced dose-response curves with significantly shallower slopes than PGF2α and were shown to be at least thirty-five times less potent than the parent compound. Therefore, oxidation of PGF2α at the carbon-15 position by 15-hydroxy prostaglandin dehydrogenase appears to produce compounds with minimal
bronchopulmonary activity. 相似文献
3.
John W. Wilks 《Prostaglandins & other lipid mediators》1982,24(6):837-842
Dose response relationships for pregnancy termination in hamsters following administration of prostaglandin F2α (PGF2α by three subcutaneous methods were determined in 526 hamsters. The median effective dose (ED50) for PGF2α given as a single subcutaneous injection in 500 μl of saline was 22.2 μg. Administration of the prostaglandin with an Alzet® osmotic minipump (subcutaneous insertion for 24 hours) required 1.35 times more PGF2α (ED50 = 30.0 μg). The least effective method of prenancy termination in the hamster involved administration of PGF2α by a single subcutaneous injection in 20.4 μl of saline (the same volume delivered by the minipump in 24 hours); the ED50 for this method of administration was 41.3 μg of PGF2α. 相似文献
4.
P.M. O'Byrne H. Aizawa R.A. Bethel K.F. Chung J.A. Nadel M.J. Holtzman 《Prostaglandins & other lipid mediators》1984,28(4)
We studied the effect of prostaglandin F2α (PGF2α) on the responsiveness of pulmonary airways in dogs. Airway responsiveness was assessed by determining the bronchoconstrictor response to increasing concentrations of acetylcholine aerosol delivered to the airways. In each of five dogs, we determined responsiveness during treatment with physiologic saline, histamine, or PGF2α aerosols. The doses of histamine and PGF2α were determined by establishing the largest dose of each which could be given to the dog without causing bronchoconstriction (subthreshold doses). We found that airway responsiveness was not significantly different during histamine treatment than after saline, however, responsiveness increased during treatment with PGF2α. In addition, the hyperresponsiveness induced by PGF2α was prevented by pretreatment with the ganglion blocking drug hexamethonium (5 mg/kg given intravenously). The results show that PGF2α specifically increases the responsiveness of pulmonary airways in doses that do not cause bronchoncostriction, and suggest that the hyperresponsiveness involves a neural mechanism such as increased responsiveness of airway sensory nerves. 相似文献
5.
Ralf G. Rahwan Franziska R. Del Vecchio Gregory Azzolin Donald T. Witiak 《Prostaglandins & other lipid mediators》1983,25(4):519-530
DIPA [5,6-bis(dibenzyloxy)-1-oxo-2-propyl-2-indanpropionic acid] was evaluated for its antiabortifacient action in mice. PGF2α administered intramuscularly twice daily at 525 μg/kg per dose starting on day-17 of gestation resulted in premature delivery (prior to day-19 of gestation) in 55% of the animals. This constituted an ED50 abortifacient dosage schedule of PGF2α. Intramuscular administration of DIPA at a dose of 50 mg/kg twice daily, starting on day-15 of gestation, protected the mice against the premature delivery induced by the ED50 dosage schedule of PGF2α in that only 20% of the animals delivered prematurely. In saline-treated controls, none of the animals delivered prior to day-19 of gestation. Thus, DIPA appears to be an effective antiabortifacient agent. 相似文献
6.
J. N. Stellflug T. M. Louis H. D. Hafs B. E. Seguin 《Prostaglandins & other lipid mediators》1975,9(4):609-615
During diestrus in three consecutive estrous cycles, each of six heifers was given (im) 30 mg, 15 mg (twice at 6-hr intervals) and 60 mg prostaglandin F2α (PGF2α) tham salt. Neither the decline in blood progesterone, the increase in blood estradiol, the duration or the peak of the LH surge, the interval to onset of estrus, nor the interval to ovulation was affected significantly by dose of PGF2α. Thus, relative to that after 30 mg PGF2α im, two injections of 15 mg at 6-hr intervals or 60 mg PGF2α did not hasten luteolysis. Thirty mg was an ample im dose of PGF2α to cause luteolysis. Regardless of im dose of PGF2α, blood PGF peaked at about 6.0 ng/ml within 10 minutes and returned to basal values (<1.0 ng/ml) within 90 minutes. In another trial, after a single iv injection of 5 mg PGF2α, blood PGF peaked (25 ng/ml) within 5 minutes and returned to basal values within 15 minutes. During a 30-minute infusion (0.5 mg/minute) of PGF2α, blood PGF plateaued at 29.5 ng/ml with a metabolic clearance rate of 17.0 liters per minute. 相似文献
7.
Dale R. Bergren Jon M. Gustafson Donna L. Myers 《Prostaglandins & other lipid mediators》1984,27(3):391-405
Pulmonary rapidly-adapting-receptors (RARs) are sensory nerve endings whose afferent fibers can be recorded in the vagus nerve. RARs may play a role in reflex bronchoconstriction as seen in anaphylaxis. They can be stimulated by chemical mediators of anaphylaxis, such as prostaglandin F2α (PGF2α). PGF2α aerosol was administered to saline and bovine serum albumin (BSA)-treated guinea pigs while recording the activity of RARs. PGF2α (250 μg/ml) given for 7–13 minutes increased both tracheal pressure and nerve activity over that produced by saline exposure in untreated guinea pigs. PGF2α administered for three minutes (5–100 μg/ml) increased RAR nerve activity in a dose-related manner in the first five minutes of the experiment only in the BSA treated guinea pigs. Since changes in tracheal pressure did not show a significant dose-response relationship, the RARs responding to PGF2α seemed to be stimulated by a direct mechanism. No correlation was shown between tracheal pressure and RAR nerve activity during PGF2α treatment. Whereas, a significant correlation was found between tracheal pressure and RAR nerve activity during histamine aerosol treatment (r=0.985). Histamine aerosol (1 to 1000 μg/ml, 3 min.) increased intratracheal pressure for 3 out of 4 doses. RAR nerve activity increased significantly only at the highest dose. Therefore, a possible direct effect of PGF2α upon RARs exists while the effect of histamine seems dependent upon changes in airway pressure in the guinea pig. 相似文献
8.
Potential interactions between PGD2 and PGF2α in the mesenteric and renal vascular beds were investigated in the anesthetized dog. Regional blood flows were measured with electromagnetic flow probes. PGD2, PGF2α and Norepinephrine (NE) were injected as a bolus directly into the appropriate artery, and responses to these agents were obtained before, during and after infusion of either PGD2 or PGF2α into the left ventricle. In each case, the infused prostaglandin caused vascular effects of its own. Left ventricular infusion of PGD2 reduced responses to local injections of PGD2 in the intestine, and a similar effect was observed for PGF2α, suggesting significant receptor or receptor-like interactions for each of the prostanoids. However, systemic infusion of prostaglandin F2α (20–100 ng/kg/min) had no effect on renal or mesenteric vascular responses to local injection of prostaglandin D2. Similarly, PGD2 administration (100 ng/kg/min) did not affect responses to PGF2α in the intestine. The present results therefore suggest that these prostaglandins, i.e., D2 and F2α, act through separate receptors in the mesenteric and renal vascular beds. In addition, increased prostaglandin F2α levels produced by infusion of F2α reduced mesenteric but not renal blood flow, suggesting that redistribution of cardiac output might participate in side effects often observed with clinical use of this prostaglandin, such as nausea and abdominal pain. 相似文献
9.
Non-esterified fatty acids (NEFA) can significantly interfere with the radioimmunoassay of PGE and PGF2α using commercially available anti-sera. PGB1 antigen-antibody binding is 50% inhibited by 110 pg of PGB1, 48 ng of PGE1, 3.5 μg of PGF2α, or 9.0 μg linoleic, 14 μg arachidonic, 22 μg δ-linoleic, 40 μg palmitoleic or 45 μg oleic acids. PGF2α antigen-antibody binding is 50% inhibited by 270 pg of PGF2α, 70 ng of PGE1, or 4.2 μg arachidonic, 14 μg δ-linolenic, 22 μg linoleic, 70 μg palmitoleic or 110 μg oleic acids. Physiological levels of NEFA, such as the quantities found in small volumes of plasma, are sufficient to prohibit accurate prostaglandin measurements. Chromatography on small columns of silicic acid proved to be an effective technique for separation of NEFA and prostaglandin from lipid extracts, however, the results of this study suggest that the interference produced by the presence of NEFA in the measurement of prostaglandin from certain physiological fluids may be avoided if the prostaglandins are not extracted prior to radioimmunoassay. 相似文献
10.
In humans eicosapentaenoic acid can be converted to 3-series prostaglandins (PGF3α, PGI3, and PGE3). Whether 3-series prostaglandins can protect the gastric mucosa from injury as effectively as their 2-series analogs is unknown. Therefore, we compared the protective effects of PGF3α and PGF2α against gross and microscopic gastric mucosal injury in rats. Animals received a subcutaneous injection of either PGF3α or PGF2α in doses raning from 0 (vehicle) to 16.8 μmol/kg and 30 min later they received intragastric administration of 1 ml of absolute ethanol. Whether mucosal injury was assessed 60 min or 5 min after ethanol, PGF3α was significantly less protective against ethanol-induced damage than PGF2α. These findings indicate that the presence of a third double bond in the prostaglandin F molecule between carbons 17 and 18 markedly reduces the protective effects of this prostaglandin on the gastric mucosa. 相似文献
11.
H. Karppanen Anna-Leena Sirn Alice Eskeli-Kaivosoja 《Prostaglandins & other lipid mediators》1979,17(3):385-394
Administration of PGF2α (0.2–6.4 μg) into the lateral cerebral ventricle (i.c.v.) induced dosedependent increases in blood pressure, heart rate and body temperature in urethane-anaesthetised rats, but had no effect on these parameters when the same dose range was administered intravenously. Peripheral pretreatment with sodium meclofenamate (50 mg/kg s.c.) shifted all the dose-response curves for PGF2α (i.c.v.) to the left, but indomethacin (50 mg/kg s.c.) did not significantly affect those changes. Central pretreatment with sodium meclofenamate or indomethacin (1.25 mg per rat i.c.v.) failed to modify significantly the effects of centrally administered PGF2α.The results support previous suggestions that PGF2α may participate in the central control of the cardiovascular and thermoregulatory systems, and also suggest that there may be differences in the sites and/or modes of action between sodium meclofenamate and indomethacin. 相似文献
12.
Dwight R. Robinson Howard Smith Mary B. McGuire Lawrence Levine 《Prostaglandins & other lipid mediators》1975,10(1):67-85
The synthesis of prostaglandins by rheumatoid synovial tissue in organ culture was studied utilizing radioimmunoassay, with antisera to PGB1, PGF1α and PGF2α. It was established that PGE2 and PGF2α were the major prostaglandins formed by analyses of culture media with the two antisera to PGF, before and after alkali treatment. Indomethacin at 5 μg/ml suppressed prostaglandin synthesis, usually to <1% of control cultures. Colchicine, 0.1 μg/ml resulted in marked stimulation of prostaglandin synthesis, in some cases over 10 fold. It is suggested, because of the colchicine effect, that the state of the microtubules may regulate the rate of prostaglandin biosynthesis. It is possible that prostaglandin E2 produced by rheumatoid synovia may contribute to the pathogenesis of the inflammatory reaction and lead to destruction of juxta-articular bone in rheumatoid arthritis. 相似文献
13.
Prostaglandin F2α (PGF2α) at 14, 30 or 50 μg/hamster/day from Days 3–5 of pseudopregnancy (PSP) shortens PSP from a mean length of 9.1 to 5.6–7.9 days, depending on the dose of PGF2α administered. Bilateral intrauterine device (BIUD) bearing hamsters exhibit a mean length of PSP of 9.2 days, which is comparable to that in normal saline controls. Combination of PGF2α (14 μg/day on Days 3–5 of PSP) and BIUD also resulted in shortening of PSP although the mean length of PSP resulted from the combined treatment was not significantly different from those PSP animals treated with 14 μg/day of PGF2α alone. It is concluded that the antifertility effect of intrauterine device possibly is attributed to a small and continuous release of PGF which interferes with the normal implantation processes but does not curtail PSP. 相似文献
14.
C.R. Pace-Asciak M.C. Carrara G. Rangaraj K.C. Nicolaou 《Prostaglandins & other lipid mediators》1978,15(6):1005-1012
Intact rings and homogenates of aorta from spontaneously hypertensive rats (SHR) contain enhanced capacity over normal rats (NR) to convert arachidonic acid into PGI2. The PGI2 synthetic system in SHR is stimulated to a greater extent than NR by norepinephrine. Indomethacin blocks this stimulation. PGE2 and PGF2α were detected in much smaller amounts in homogenates (undetected in rings) but their formation was not enhanced by the hypertensive tissue. The identity of PGI2 was based on 1) direct pharmacological assay on the rat blood pressure. In this system identical vasodepressor responses to PGI2 are observed after intracarotid and intrajugular administration 2) indirectly as 6-keto PGF1α isolated after incubation of aortic homogenates with tritiated arachidonic acid and 3) indirectly by GC-MS assay of PGE2, PGF2α and 6-keto PGF1α formed during incubation of aortic homogenates with excess unlabeled arachidonic acid. These results provide additional support to our recent hypothesis that PGI2, of aortic origin, might actively participate in the regulation of systemic blood pressure. Its enhanced formation by intact hypertensive vascular tissue reflects an increase in the number of enzyme molecules immediately available to the substrate. This could probably be an adaptive response to the elevated levels of catecholamines in the circulation. 相似文献
15.
Dwight R. Robinson Howard Smith Mary B. McGuire Lawrence Levine 《Prostaglandins & other lipid mediators》1975,10(4):67-85
The synthesis of prostaglandins by rheumatoid synovial tissue in organ culture was studied utilizing radioimmunoassay, with antisera to PGB1, PGF1α and PGF2α. It was established that PGE2 and PGF2α were the major prostaglandins formed by analyses of culture media with the two antisera to PGF, before and after alkali treatment. Indomethacin at 5 μg/ml suppressed prostaglandin synthesis, usually to <1% of control cultures. Colchicine, 0.1 μg/ml resulted in marked stimulation of prostaglandin synthesis, in some cases over 10 fold. It is suggested, because of the colchicine effect, that the state of the microtubules may regulate the rate of prostaglandin biosynthesis. It is possible that prostaglandin E2 produced by rheumatoid synovia may contribute to the pathogenesis of the inflammatory reaction and lead to destruction of juxta-articular bone in rheumatoid arthritis. 相似文献
16.
The mechanism of stimulatory and inhibitory action of PGF2α on ovarian steroidogenesis both under
and
conditions has been studied in the pseudo-pregnant rabbits. Short term incubation of the ovaries with PGF2α (2.82 × 10−5M) resulted in an increased synthesis of progesterone and 20α-OH P. The addition of PGF2α in the medium and further incubation of the ovaries obtained from rabbits that had been constantly infused with PGF2α (0.5 μg/min.) for two hours resulted in increased synthesis of these progestins. The ratio of progesterone to 20α -OH P was also enhanced under these conditions and thus supported the luteotropic action of small doses of PGF2α under short term incubations. However, as the amount of PGF2α infused was increased to 5 μg/min., the addition of PGF2α under
conditions strikingly decreased the production of these progestins. The ratio of progesterone to 20α -OH P was also decreased and thus was indicative of luteolytic action of higher doses of PGF2α. High doses of PGF2α (5.64 × 10−4M) failed to I cause any significant change in the progestin synthesis under short term incubation. These results thus suggest that the luteotropic and luteolytic action of PGF2α in the luteinized rabbit ovary is dose and time dependent. 相似文献
17.
The effect of prostaglandin F2α(PGF2α) on endocrine and ovarian function during the early luteal phase of the domestic cat was investigated. Queens were induced to ovulate and then injected subcutaneously with 0.5–5.0 mg PGF2α/kg body weight. The greatest dose was found to approach toxicity. Concentrations of progesterone were similar in cats following treatment with PGF2α compared to values of controls. Development and regression of corpora lutea as determined by serial laparoscopy were similar in all groups. These data indicate that PGF2α at the tested dosages, given during the early luteal phase is not luteolytic in this species and suggest that these regimens would be ineffective for the premature termination of pseudopregnancy. 相似文献
18.
Prostaglandin F2α (PGF2α) has been shown to be an effective stimulant of hepatic bile flow producing a specific chloride rich bile. Subsequent evaluation by radioimmunoassay has shown that prostaglandin F compounds are present in relatively large amounts in canine hepatic bile. This study evaluates the effect of PGF2α administration and of prostaglandin synthetase inhibition by aspirin and indomethacin on bile flow and radioimmunoassayable prostaglandin F (iPGF) secretion. Chronic, canine bile fistula preparations were utilized and the enterohepatic circulation was maintained by intravenous bile salts. Bile volume and composition were evaluated by standard techniques as well as bile PGF concentration by radioimmunoassay during bile salt infusion and during bile salt and PGF2α, aspirin and indomethacin infusion in varying doses. Both aspirin and PGF2α were potent stimulatns of hepatic bile flow with aspirin producing a chloride rich bile similar to that produced by PGF2α. PGF2α produced dose related increases in bile iPGF concentration and output indicating that as the systemic concentration increases during infusion of PGF2α the lipid appears in bile. Aspirin in the highest dose administered, decreased iPGF concentration in bile while output was unchanged. Indomethacin was ineffectual in consistently altering bile flow or iPGF secretion. This study demonstrates that iPGF is present in canine bile, that its concentration can be altered by prostaglandin infusion while prostaglandin synthetase inhibition has minimal effects on bile iPGF secretion. 相似文献
19.
W. Russell 《Prostaglandins & other lipid mediators》1975,10(1):163-183
Non-pregnant pigtail monkeys (M. nemestrina) were given ICI 80996 subcutaneously and ICI 81008 and PGF2α subcutaneously or intravaginally, once daily on days 20–30 inclusive, or two or three times on days 24 or 26 only. Doses of 50 μg/kg of ICI 80996, 100 μg/kg of ICI 81008 and approx. 1 mg/kg of PGF2α were used.In the majority of monkeys treated subcutaneously a rapid fall in circulating progesterone concentrations and earlier than normal menstrual bleeding occurred. When given per vaginam, ICI 81008 was as effective as when given subcutaneously, though PGF2α was less effective intravaginally than by the subcutaneous route. 相似文献
20.
Anders gmo 《Prostaglandins & other lipid mediators》1975,9(3):451-457
PGE1(50μg/animal) and PGF2α (250 μg/animal) caused a transient in serum LH at 5 min after injection. PGE1 (250 μg/animal) had a biphasic effect on serum LH. A small peak was obtained at 5 min, and a second, larger peak at 60 min after injection. It is suggested that the first peak is a result of the stress associated with injection of the PGs, whereas the second peak represents a physiological effect of PGE. Subcutaneous injection of PGE1 (1 mg in arachis oil b.i.d.) for 10 days did not affect the concentration of LH in serum, the function of the accessory sexual glands or the sexual activity. PGF2α, given at the same dose and in the same manner, increased the sexual activity but left all other variables unaffected. The pituitary responsiveness to LH-RH was unaltered by the treatment with PGE1 and PGF2α. 相似文献