Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Endothelial cells synthesize prostacyclin (PGI(2)), an unstable prostaglandin that inhibits platelet aggregation and serotonin release. Because cyclooxygenase, which is necessary for synthesis of PGI(2), is inactivated by aspirin, we examined the effect of aspirin on PGI(2) production by cultured human endothelial cells. Endothelial cells synthesize PGI(2) (20.1+/-7.2 ng/10(6) cells, mean+/-SD) when stimulated with 20 muM sodium arachidonate for 2 min. PGI(2) production is inhibited by low-dose aspirin (5 muM); the t((1/2)) of inactivation is 6.0+/-1.3 min (mean+/-SEM, n = 3). Thus, endothelial cell cyclooxygenase is as sensitive to aspirin as the enzyme in platelets. After 1 h incubation with aspirin, endothelial cell PGI(2) production was inhibited 50% by 2.1+/-0.4 muM aspirin and was inhibited 90% by 6.2+/-0.9 muM aspirin (mean+/-SEM, n = 4). When endothelial cells were incubated with 100 muM aspirin, washed, and recultured, their ability to synthesize PGI(2) returned to control levels in 35.6+/-1.0 h (mean+/-SEM, n = 4). Recovery of endothelial PGI(2) production after aspirin depended on de novo protein synthesis because treatment with cycloheximide (3 mug/ml) inhibited recovery by 92%.These results indicate that although endothelial cell cyclooxygenase in vitro is inhibited by low concentrations of aspirin, endothelial cells rapidly resynthesize their cyclooxygenase after the aspirin is removed. This rapid resynthesis of cyclooxygenase lessens the likelihood that aspirin used in clinical doses promotes thrombosis.
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PMID:Recovery of endothelial cell prostacyclin production after inhibition by low doses of aspirin. 37 42

Aspirin at high but not at low doses reduces the fibrinolytic response to venous occlusion. Inhibition of vascular prostacyclin synthesis could be involved in this effect. Fish oil supplementation may redirect prostanoid metabolism toward an overall "antithrombotic" condition but with controversial effects on prostacyclin formation. In this study we investigated the effect of low-dose aspirin together with n-3 polyunsaturated fatty acid (PUFA) supplementation on the fibrinolytic response to venous occlusion. Following a double-blind, randomized, crossover design, six healthy volunteers (three men and three women, 24-37 years old) were given for 29 days 5.3 g eicosapentaenoic and docosahexaenoic acids or a corresponding dose of n-6 PUFAs as control; aspirin (40 mg/day) was then added for an additional 14 days. A 2-month washout period was allowed before the crossover. Blood was collected before and after venous stasis on days 0, 29, and 43 of each test period. A combination of aspirin with n-3 PUFAs reduced the fibrinolytic response to venous occlusion in all subjects, the mean value of fibrinolytic activity after stasis being 240 +/- 40 mm2, a value significantly lower than at baseline (366 +/- 51 mm2, mean +/- SEM, p < 0.05). Similarly, the tissue-type plasminogen activator (t-PA) antigen level was lower in the aspirin + PUFA-treated group. Plasminogen activator inhibitor activity before stasis was enhanced by n-3 PUFA supplementation (from 7.5 +/- 2 to 14.8 +/- 3 IU/ml, p < 0.05), an effect not affected by aspirin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Modulation of fibrinolytic response to venous occlusion in humans by a combination of low-dose aspirin and n-3 polyunsaturated fatty acids. 139 May 91

The effects of lung traction on arterial blood pressure and plasma prostacyclin concentrations were studied in five patients undergoing partial pneumonectomy or lobectomy. After manual traction of a lung segment, mean arterial blood pressure decreased from 77 +/- 5 mm Hg (mean +/- SEM, before lung traction) to 59 +/- 5 mm Hg. The concentrations of 6-keto prostaglandin F1 alpha (a stable breakdown product of prostacyclin) increased significantly from 46 +/- 6 pg/mL (mean +/- SEM, before thoracotomy) to 593 +/- 91 pg/mL. Four of five patients showed facial flushing and palmar erythema. Arterial blood pressure returned to pretraction value, and both the facial flushing and palmar erythema disappeared within 30 min after lung traction. These results suggest that traction of the lung stimulates release and/or production of prostacyclin, which results in facial flushing, palmar erythema, and decrease in arterial blood pressure.
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PMID:Lung traction causes an increase in plasma prostacyclin concentration and decrease in mean arterial blood pressure. 141 33

Recently we demonstrated that the vascular response to angiotensin II (A-II) was attenuated in an endothelium-dependent manner by using the isolated ring specimen iliac arteries of pregnant rabbits. In this paper we investigated the possibility that three vasoactive substances, thromboxane A2(TXA2), prostacyclin (PGI2), and endothelium-derived nitric oxide (EDNO), might be involved in this refractoriness to A-II during pregnancy, by measuring the changes in the vascular response to A-II (pA2, intrinsic activity) of the isolated arterial rings of rabbits before and after the addition of an inhibitor specific for each of these three substances. Sodium ozagrel, TXA2 synthetase inhibitor, decreased the vascular response to A-II more in the blood vessels of pregnant rabbits, regardless of whether the endothelium was intact or denuded, than in the blood vessels of non pregnant rabbits. Tranylcypromine, a PGI2 synthetase inhibitor, significantly increased contractility in the blood vessels with intact endothelium of pregnant rabbits (i.a. = 1.39 +/- 0.099, n = 11, mean +/- SEM), compared to that in the blood vessels with intact endothelium of non pregnant rabbits (i.a. = 1.08 +/- 0.090, n = 7). Methylene blue, a guanylate cyclase inhibitor which blocks the effect of EDNO, amplified the vascular response in blood vessels with intact endothelium of both groups, and more intensely in the blood vessels of pregnant rabbits.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Effect of endothelium-derived nitric oxide and prostaglandins on the endothelium-dependent vascular refractoriness to angiotensin II in pregnant rabbits]. 145 44

Prostaglandins circulating in the maternal and foetal blood have been implicated in important physiological systems. These functions include foetal adrenal function, maintenance of patency of the ductus arteriosus, regulation of uterine and umbilical circulations, and labor and delivery type myometrial contractions. The placenta is a major site of prostaglandin production in pregnancy. Limited data are available which combine measurements of veno-arterial differences across the uterine and umbilical circulations with blood flow in these circulations to enable calculation of umbilical-placental and utero-placental production rates for the prostaglandins. In chronically instrumented pregnant ewes, between 129 and 136 days of gestation, prostaglandin F2 alpha(PGF2 alpha), 13, 14 dihydro-15-keto prostaglandin F2 alpha (PGFM), prostaglandin E2 (PGE2) were measured in the maternal carotid artery and uterine vein. Foetal PGE2, and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) (the major metabolite of prostacyclin) were measured in umbilical venous and foetal descending aorta arterial plasma. Umbilical and uterine blood flow were measured using the diffusion-equilibrium technique. Uterine blood flow was 1693 +/- 137 ml.min-1 (mean +/- SEM); uterine production rates were 480 +/- 88 ng.min-1 for PGF2 alpha, 517 +/- 144 ng.min-1 for PGFM, and 165 +/- 27 ng.min-1 for PGE2. Umbilical blood flow was 147 +/- 17 ml.min-1.kg-1 foetal body weight. Umbilical production rates into the foetal circulation were 11 +/- 2 ng.min-1.kg-1 for PGE2 and 6 +/- 2 ng. ng.min-1.kg-1 foetal body weight for PGI2.
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PMID:Prostaglandin production in the umbilical and uterine circulations in pregnant sheep at 129-136 days gestation. 150 Jun 35

In normal pregnancy, increased production of platelet thromboxane A2(TXA2) parallels increased biosynthesis of vascular prostacyclin (PGI2). An imbalance in the formation of these prostaglandins is believed to be associated with the pathogenesis of pregnancy-induced hypertension (PIH). Recent evidence suggested that aspirin in low doses was effective in reducing the incidence of PIH, by selective inhibition of platelet-derived TXA2 biosynthesis. In this communication, we determined the urinary 11-dehydro TXB2 and 6-keto-PGF1 alpha, which are major metabolites of TXA2 and PGI2, respectively, from early to late pregnancy of normal pregnant women and of women complicated with PIH. The ratio of 11-dehydro TXB2 to 6-keto-PGF1 alpha decreased significantly from as early as 10wks of gestation when compared with that in non-pregnant controls (1.43 +/- 0.15 vs 1.99 +/- 0.13: Mean +/- SEM, p less than 0.05), and increased in later pregnancy to the control values at term. No significant difference was found in the excretion of 11-dehydro TXB2 between normal pregnant women and women with PIH. In contrast, urinary excretion of 6-keto-PGF1 alpha decreased in women with PIH. The ratio of 11-dehydro TXB2 to 6-keto-PGF1 alpha increased significantly as compared with that of pregnant controls. These results demonstrated that disturbed production of vascular PGI2 may be the primary cause of PIH, and affect the vascular responsiveness to pressor inducers such as angiotensin II.
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PMID:[Urinary 11-dehydrothromboxane B2 and 6-keto-prostaglandin F1 alpha in normal pregnant women and in women complicated with pregnancy-induced hypertension]. 150 26

To investigate the role of thromboxane (Tx) A2 and prostaglandin (PG) I2 in the development of airway responsiveness after ozone exposure, we measured the airway responsiveness to inhaled methacholine (Mch), TxB2 and 6-keto-PGF1 alpha levels in bronchoalveolar lavage fluid (BALF) in 18 dogs after ozone exposure. Airway responsiveness to Mch was determined by Astograph (7 Hz oscillation method), and ozone exposure was carried out for 2 hr at an ozone level of 3.01 +/- 0.05 ppm (mean +/- SEM). Airway responsiveness to Mch increased significantly after ozone exposure (p less than 0.001). TxB2 levels in BALF were not affected by ozone exposure, but the levels of 6-keto-PGF1 alpha decreased significantly after ozone exposure (p less than 0.001). The ratio of TxB2/6-keto-PGF1 alpha increased significantly after ozone exposure, and the change in this ratio correlated significantly with the change of airway responsiveness to Mch (p less than 0.01, r = 0.654). These results suggest that airway hyperresponsiveness after ozone exposure is induced by the relative increase of TxA2 due to the decrease of PGI2.
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PMID:[Role of thromboxane A2 and prostaglandin I2 in the increase of airway responsiveness in dogs after ozone exposure]. 152 68

We evaluated the inhibitory effect of S-1452, a specific thromboxane (Tx) A2 receptor antagonist on the increase of airway responsiveness in 7 dogs after ozone exposure. Airway responsiveness to inhaled methacholine (Mch) was determined by Astograph (7 Hz oscillation technique), and at the same time TxB2, 6-keto-prostaglandin (PG) F1 alpha, PGE2 levels and total cell counts in the bronchoalveolar lavage fluid (BALF) were measured. Ozone exposure was carried out for 2 hr at an ozone level of 3.04 +/- 0.02 ppm (mean +/- SEM). Airway responsiveness to Mch increased significantly after ozone exposure (p less than 0.01), and this hyperresponsiveness was inhibited significantly by pretreatment with S-1452 (p less than 0.02). TxB2 and PGE2 levels in BALF did not change after ozone exposure, but the levels of 6-keto-PGF1 alpha decreased significantly after ozone exposure (p less than 0.05). Total cell counts in BALF increased significantly after ozone exposure (p less than 0.02). The decrease of 6-keto-PGF1 alpha levels and the increase of total cell counts were not affected by pretreatment with S-1452. These results suggest that S-1452 is protective against the increase of airway responsiveness induced by ozone exposure, and that TxA2 plays an important role in the hyperresponsiveness. But hyperresponsiveness may not be induced by hyperproduction of TxA2, but by the relative increase of TxA2 to PGI2.
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PMID:[Inhibitory effect of S-1452, a specific thromboxane A2 receptor antagonist on the increase of airway responsiveness in dogs after ozone exposure]. 153 11

Angioplasty is considered as an alternative to surgical reconstruction of arteriosclerotic vessels especially since lasers and atherectomy devices have become clinically available. However, the resulting arterial injury may lead to acute thrombotic occlusion and chronic restenosis because of hyperplastic vascular repair. The purpose of this experimental study was to evaluate the consequences of thermal laser arterial injury on platelet deposition and myointimal hyperplasia in dog femoral arteries. An intraarterial, short-term prostacyclin (PGI2) infusion was given to evaluate the antithrombotic and antiproliferative effects of this drug. Severe arterial necrosis, partly carbonized and vacuolized, extending to the adventitia was induced by a transluminal heated laser probe motion. The platelet deposition after one hour was 33.62 +/- 6.56 (x 10(6)/cm2.) (mean +/- SEM) without prostacyclin, after 40 ng/kg/min prostacyclin (PGI2) 24.70 +/- 5.45 and after 400 ng/kg/min 9.3 +/- 2.26 (p less than 0.005 no PGI2 vs 400 ng/kg/min PGI2). Myointimal hyperplasia was present eight weeks after thermal laser vascular injury independent of the initially administered prostacyclin. In conclusion, acutely thrombotic and chronically hyperplastic femoral arteries were found following transluminal thermal arterial injury in dogs. Prostacyclin administration could be clinically beneficial in reducing acute vascular thrombosis following thermal angioplasty. Short-term use of this substance, however, may not prevent a hyperplastic response to angioplasty.
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PMID:Thermal laser arterial injury and prostacyclin administration in dogs: thrombotic and hyperplastic consequences. 160 23

The levels of prostaglandin (PG) E2 and 6-keto-PGF1 alpha (stable metabolite of prostacyclin) in plasma and gastric juice were determined in 113 critically ill children and adolescent, and compared to those registered in a plasma control group of 24 children and a gastric juice control group of 15. The gastric juice concentration of PGE2 is our patients [9.2 +/- 3.1 (SEM) pg/ml] was significantly lower (p = 0.001) than in the control group [81.1 +/- 18.1 (SEM) pg/ml]. There were no differences in plasma levels of PGE2 and plasma gastric juice levels of 6-keto-PGF1 alpha between the patients and the control groups. Children who died had lower plasma levels of PGE2 [6.2 +/- 2.2 (SEM) pg/ml] and gastric juice levels of PGE2 [2.3 +/- 0.8 (SEM) pg/ml] than the survivors (p less than 0.05). The gastric juice concentration of PGE2 was also lower in children who suffered important upper gastrointestinal bleeding, although the difference did not reach statistical significance.
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PMID:Plasma and gastric juice levels of prostaglandins in critically ill children. 161 33


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