Comparison of umbilical vein models for measurement of relative prostacyclin and thromboxane production

There is growing evidence that blood vessels generate TXA2 in addition to PGI2. We examined effluents from continuously perfused human umbilical vein and supernatants from umbilical vein rings for TXB2 and 6-keto-PGF1 alpha measurements (stable metabolites of TXA2 and PGI2, respectively). TXB2 and 6-keto-PGF1 alpha were identified in all samples. 6-keto-PGF1 alpha to TXB2 ratio was higher in intact vein effluents than in the venous ring supernatants (112:1 and 28:1, respectively, P less than 0.01). Arachidonate stimulation increased 6-keto-PGF1 alpha and TXB2 levels similarly in the intact vein effluent. In contrast, stimulation of the venous rings resulted in a relatively larger increase in TXB2 than in 6-keto-PGF1 alpha. This caused 6-keto-PGF1 alpha to TXB2 ratio to decline (p less than 0.01). The identity of TXB2 was confirmed in several different ways. These data suggest that 1) human umbilical veins produce TXA2 in addition to PGI2, 2) TXA2 release is more by venous rings than by the intact vein probably reflecting contribution from non-endothelial layers, and 3) arachidonate stimulation causes relatively greater release of TXA2 than of PGI2 from the venous rings, whereas release of PGI2 and TXA2 is similar from the intact vein.     

Prostacyclin and thromboxane formation in human umbilical arteries following stimulation with vasoactive autacoids

The formation of prostacyclin (PGI2) and thromboxane A2 (TXA2) (measured as the stable metabolites 6-keto-PGF1 alpha and TXB2) during stimulation with vasoactive autacoids was registered in human umbilical arteries perfused in vitro. Responses were registered within 3-4 minutes after addition of the substances. Both angiotensin I and II were found to increase the formation of PGI2 while depressing that of TXA2. Serotonin increased the formation of TXA2 but not that of PGI2. Both PGE2 and PGF2 alpha stimulated the PGI2 formation. The TXA2 mimetic U46619, increased PGI2 production, whereas PGI2 slightly increased the formation of TXA2. All responses were found to be completely inhibited by indomethacin.     

Myocardial prostacyclin and thromboxane A2 synthetase activities during ischemia and reperfusion in isolated rabbit heart

The aim of the study was to determine the prostacyclin (PGI2) and thromboxane A2 (TXA2) synthetase activities of myocardial tissue and their variation during ischemia and reperfusion. Regional ischemia was induced by 10 min occlusion of the left anterior descending coronary artery in isolated Langendorff rabbit hearts. Biosynthesis of PGI2 and TXA2 were carried out by using arachidonic acid as substrate and left ventricle microsomes (LVM) from ischemic and non-ischemic areas as sources of PGI2 and TXA2 synthetase. 6-keto-PGF1 alpha and TXB2, stable metabolites of PGI2 and TXA2 respectively, were determined by radioimmunoassay. Experiments carried out under the adopted conditions showed that LVM were able to synthetise PGI2 as well as TXA2 from arachidonic acid. On the other hand, ischemia depressed both PGI2 and TXA2 synthetase activities of cardiac tissue: the depression was more pronounced on TXA2 synthetase than on PGI2 synthetase with no significant difference between ischemic and non-ischemic regions. Moreover, ischemia increased the ratio 6-keto-PGF1 alpha/TXB2 indicating therefore that it can facilitate the formation of PGI2. The post ischemic reperfusion of the heart counteracted the decrease in PGI2 synthetase induced by ischemia which returned to the normal level: reperfusion also slightly reversed the decrease in TXA2 the decrease in TXA2 synthetase. However, the diminution in TXA2 synthetase of non-ischemic myocardium was attenuated but it remained lower than the normal level. These results suggested that the whole left ventricle is affected by regional ischemia. Furthermore it appears that myocardial TXA2 synthetase is more vulnerable than PGI2 synthetase to a lack of oxygen and nutrients.     

Effect of dipyridamole on prostaglandin generation by human platelets and vessel walls

These experiments were conducted to determine the effects of dipyridamole on human platelet aggregation, platelet thromboxane A2 (TXA2) and human vessel wall prostacyclin (PGI2) generation. Dipyridamole in varying concentrations (5 to 50 micrograms/ml) had no direct effect on ADP-induced platelet aggregation in vitro, but it potentiated PGI2-induced platelet aggregation inhibition at these concentrations. Dipyridamole also inhibited arachidonic acid-induced platelet TXA2 generation at these concentrations. In continuously perfused umbilical vein segments, dipyridamole treatment resulted in stimulation of PGI2 release determined by bioassay and by measurement of its stable metabolite 6-keto-PGF1 alpha. Minimum concentration of dipyridamole causing PGI2 release was 50 micrograms/ml. These in vitro studies suggest that anti-thrombotic effects of dipyridamole in man are mediated mainly by potentiation of PGI2 activity and to some extent by TXA2 suppression. Stimulation of PGI2 release by human vessels may not be seen in usual therapeutic concentrations.     

Up-regulation of endothelial cyclooxygenase-2 and prostanoid synthesis by platelets. Role of thromboxane A2

Platelet-vascular endothelial cell interactions are central to the maintenance of vascular homeostasis. Thromboxane A2 (TXA2) and prostacyclin (prostaglandin (PG)I2) are the major products of cyclooxygenase (COX) metabolism by platelets and the vascular endothelium, respectively. Here we report the effects of platelet-endothelial interactions on human umbilical vein endothelial cells (HUVECs) COX-2 expression and prostanoid synthesis. Co-incubation of platelets with HUVECs resulted in a dose-dependent induction in COX-2 expression. This was accompanied by a relatively small increase in thromboxane B2 synthesis (2 ng) by comparison to the production of 6-keto-PGF1alpha and PGE2, which increased by approximately 14 and 12 ng, respectively. Abrogation of platelet-HUVEC interactions excluded direct cell-cell contact as a required event. Preincubation of HUVECs with SQ29548, a TXA2 receptor antagonist, dose-dependently inhibited platelet-induced COX-2 expression and prostanoid synthesis. Similarly, if platelet TXA2 synthesis was inhibited no induction of COX-2 was observed. Furthermore, a TXA2 analog, carbocyclic TXA2, induced HUVEC COX-2 expression and the synthesis of 6-keto-PGF1alpha and PGE2. This was also associated with an increase in the expression and activity of PGI synthase and PGE synthase but not TX synthase. Platelet co-incubation (or TXA2) also selectively activated the p44/42 mitogen-activated protein kinase pathway to regulate HUVEC COX-2 expression. Thus it seems that platelet-derived TXA2 can act in a paracrine manner to up-regulate endothelial COX-2 expression and PGI2 synthesis. These observations are of particular importance given the recent observations regarding selective COX-2 inhibitors and the suppression of PGI2 synthesis.     

An imbalance between prostacyclin and thromboxane in relation to cerebral blood flow in neonates with maternal preeclampsia.

OBJECTIVE: A disturbance of prostacyclin (PGI2) and thromboxane A2 (TXA2) balance has been reported in preeclampsia. However, little is known about the concentrations of these prostanoids in neonates born to preeclamptic pregnant women. The purpose of this study is to determine whether the PGI2 and TXA2 concentrations are altered and whether the prostanoid balance correlates to the cerebral blood flow in neonates born to preeclampsia. METHODS: Spontaneously voided urine samples were collected from 20 neonates of normotensive and 16 neonates of preeclamptic women during the first 24 h after birth. We measured by radioimmunoassay the concentrations of urinary 6-keto-prostaglandin F1alpha (6-keto-PGF1alpha) and 11-dehydro-thromboxane B2 (11-dehydro-TXB2), respectively. Blood flow velocity in the middle cerebral artery was studied by pulsed Doppler ultrasonography in the neonates between 17 and 38 h after birth. RESULTS: There was no significant difference between the urinary 6-keto-PGF1alpha in the neonates of mothers with and without preeclampsia (median, 5.3 vs. 3.6 ng/mg of creatinine). In contrast, the urinary 11-dehydro-TXB2 and the ratio of 11-dehydro-TXB2 to 6-keto-PGF1alpha in the neonates of mothers with preeclampsia were significantly lower as compared with the neonates without preeclampsia, respectively (13.7 vs. 20.6 ng/mg of creatinine and 3.0 vs. 5.2, median). The resistance index in the middle cerebral artery was significantly reduced in the neonates with preeclampsia than without preeclampsia (0.67 +/- 0.01 vs. 0.74 +/- 0.02, mean +/- SEM). CONCLUSIONS: There was an association between maternal preeclampsia and the imbalance in the neonatal urinary excretion of PGI2 and TXA2 metabolites. This imbalance may contribute to the regulation of cerebral blood flow.     

Production of prostacyclin, 6-keto-PGF1 alpha and thromboxane B2 by incubated samples of umbilical vessels: a comparison of methods for expressing the results on dry weight, wet weight, protein or DNA bases

The production of PGI2 (determined by bioassay), and of 6-keto-PGF1 alpha and TXB2 (determined by radioimmunoassay) by samples of human umbilical vessels have been measured. The results have been calculated on four bases: dry weight, wet weight, protein and DNA. There was a higher production of PGI2 and 6-keto-PGF1 alpha by umbilical veins than by umbilical arteries; no significant difference in TXB2 production was observed between umbilical veins and arteries. The ratio of 6-keto-PGF1 alpha: TXB2 production was about 100 for the samples of veins and about 40 for the samples of arteries. The best methods of expressing the results were on the bases of protein and DNA, the latter basis being marginally the best. The least satisfactory method for expressing the results was that based on dry weight. The physiological and practical implications of the results are discussed.     

Thromboxane blockade reduces blood pressure and progression of renal failure independent of endothelin-1 in uremic rats

This study was designed to investigate the role of eicosanoids, thromboxane A2 (TXA2) and prostacyclin (PGI2) as well as their relationship with endothelin-1 (ET-1) in the pathogenesis of renal parenchymal hypertension. Uremic rats were prepared by renal mass ablation and compared with sham-operated controls. The stable metabolites of TXA2 (TXB2) and PGI2 (6-keto-PGF1alpha) and immunoreactive ET-1 concentrations were measured by specific RIAs in biological fluids and in vascular and renal tissues. To investigate the functional role of TXA2 in the progression of hypertension and renal failure, a group of uremic rats were treated with ridogrel (25 mg/kg/day), a TXA2 synthase inhibitor and receptor antagonist. Renal preproET-1 expression was assessed by Northern blot analysis. Systolic blood pressure (SBP), serum creatinine and proteinuria were found to be higher in uremic rats as compared to sham-operated controls (P < 0.01). TXB2 and ET-1 concentrations were increased in blood vessels, the renal cortex and in urine (P < 0.05). 6-keto-PGF1alpha concentrations were also increased in blood vessels and the renal cortex but decreased in urine (P < 0.05). Ridogrel significantly lowered SBP and proteinuria (P < 0.05) and blunted the increase of serum creatinine. Treatment with ridogrel resulted in a marked fall in vascular, renal and urine TXA2 concentrations, while ET-1 and 6-keto-PGF1alpha concentrations remained unchanged. The preproET-1 expression was higher in uremic rats than in the controls and was unaffected by ridogrel. These results suggest that TXA2 is involved in the pathogenesis of hypertension and renal failure progression in rats with subtotal 5/6 nephrectomy and that this effect is independent of the ET-1 system.     

水钠负荷对血,肾脏前列环素,血栓素A2的影响及...

For evaluating the role of prostacyclin (PGI2) and thromboxane A2 (TXA2) in the metabolism of salt and water, the metabolic products of PGI2 and TXA2 (6-keto-PGF1 alpha and TXB2 respectively) were measured by radioimmunoassay in salt-loaded rabbits. 36 normal rabbits were randomly divided into 3 groups: 1. normal control group; 2. 3h salt-loading group (3 h group); 3. 24 h salt-loading group (24 h group). Both the 3 h and 24 h groups were given 0.9% NaCl solution by subcutaneous injection to the hind legs. The kidneys were dissected into 4 slices: outer cortex, inner cortex, outer medulla and inner medulla. The plasma 6-keto-PGF1 alpha in the 3 h group was increased from the control value of 46.61 +/- 19.04 pg/ml to 111.63 +/- 58.36 pg/ml (P less than 0.01). All of the dissected renal slices also showed significant increase of 6-keto-PGF1 alpha synthesis in both the 3 h and the 24 h groups (P less than 0.001 vs. normal). The urinary sodium concentrations have a good correlation with 6-keto-PGF1 alpha in plasma or in kidney tissues. Plasma TXB2 in normal group was 499.27 +/- 197.86 pg/ml, but no significant change was found in the 3h group. However, in the 24 h group it decreased significantly to 218.76 +/- 114.54 pg/ml (P less than 0.05 vs. normal group). Although the TXB2 increment was significant only in inner medulla, all other dissected renal slices showed some increase of TXB2 synthesis too. It is concluded that salt-loading can cause increase of PGI1 and TXA2 synthesis in normal renal tissues.(ABSTRACT TRUNCATED AT 250 WORDS)     

Atherosclerosis decreased prostacyclin formation in rabbit lungs and kidneys.

Metabolism of arachidonic acid (AA) was studied in perfused lungs and kidneys of normal and atherosclerotic rabbits by determination of PGE2, PGF2 alpha and the stable metabolites of PGI2 (6-keto-PGF1 alpha) and TXA2 (TXB2). PGI2 was the main AA metabolite formed by normal lungs and kidneys. Atherosclerosis reduced the formation of PGI2 by about 50 % in both organs. TXA2 formation was similarily decreased in lungs. In kidneys, the decrease in PGI2 formation was accompanied by an increase in PGE2 formation.     

Metabolism of prostaglandin endoperoxide by microsomes from cat lung

It has been reported that the prostaglandin (PG) precursor, arachidonic acid, produces divergent hemodynamic responses in the feline pulmonary vascular bed. However, the pattern of arachidonic acid products formed in the lung of this species is unknown. In order to determine the type and activity of terminal enzymes in the lung, prostaglandin biosynthesis by microsomes from cat lung was studied using the prostaglandin endoperoxide, PGH2, as a substrate. The major products of incubations of PGH2 with microsomes were thromboxane (TX) B2 (the major metabolite of TXA2), 6-keto-PGF1 alpha (the breakdown product of PGI2) and 12L-hydroxy-5,8,10-heptadecatrienoic acid (HHT). Formation of TXB2 was markedly reduced by imidazole. Tranylcypromine decreased the formation of TXB2 and HHT and inhibited the formation of 6-keto-PGF1 alpha. At low PGH2 concentrations, equal production of TXB2 and 6-keto-PGF1 alpha was observed. However, as PGH2 concentration increased, 6-keto-PGF1 alpha production approached early saturation while TXB2 production increased in a linear fashion. These results suggest that enzymatic formation of TXA2 and PGI2 is a function of substrate availability in the lung. These findings provide a possible explanation for the divergent hemodynamic responses to arachidonic acid infusions at high and low concentrations in the feline pulmonary vascular bed.     

Differential effects of megavitamin E on prostacyclin and thromboxane synthesis in streptozotocin-induced diabetic rats

Diabetic subjects tend to develop microvascular complications believed to be due to platelet hyperaggregability. This increased platelet sensitivity is though to be the result of an imbalance of PGI2 and TXA2 production in diabetes. This study sought to determine whether megavitamin E supplementation could restore PGI2/TXA2 balance in streptozotocin-diabetic rats. Endogenous release of PGI2 by isolated aorta, determined via radioimmunoassay of its stable metabolite, 6-keto-PGF1 alpha, was significantly greater (P less than 0.05) in rats receiving 100x the normal vitamin E requirement than in untreated diabetic rats. PGI2 synthesis was negatively correlated with plasma glucose levels (r = -0.87, P less than 0.05) in non-fasted rats at sacrifice. Vitamin E supplementation, at both the 10x and the 100x level, significantly depressed (P less than 0.05) thrombin-stimulated synthesis of TXA2 in washed platelet. PGI2 and TXA2 production were expressed as a ratio. Megavitamin E therapy appears to increase this ratio over that seen in the diabetic animal. The data suggest that vitamin E, at high levels, exerts an ameliorating influence of the PGI2/TXA2 imbalance of diabetes.     

Cocaine use and its effect on umbilical artery prostacyclin production

Cocaine's association with adverse perinatal outcome has been attributed to its inhibition of norepinephrine uptake. This study examined the effect of cocaine on umbilical artery prostacyclin (PGI2) production. Umbilical arteries from pregnant cocaine users and controls were incubated in vitro and PGI2 levels in the media determined by measuring its stable metabolite, 6-keto-PGF1 alpha, by RIA. Cocaine users showed a significant decrease (p less than .05) in PGI2 production from their umbilical arteries when compared to controls. This appears to be through a direct effect of cocaine, as it decreases PGI2 production when added in vitro to umbilical arteries from controls. In addition, in vitro phospholipase A2 activity is inhibited by cocaine in a dose-dependent manner. These results suggest that the adverse perinatal outcome associated with cocaine use may be due in part to reduced vascular PGI2 production in the fetus.     

Studies of the mechanisms involved in the fate of prostacyclin (PGI2) and 6-keto-PGF1alpha in the pulmonary circulation.

We have investigated the metabolism of [3]H-prostaglandin (PG)I2 and its non-enzymatic breakdown product [3]H-6-keto-PGF1alpha 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 beta-NAD, [3]H-PGI2 was extensively degraded into at least one metabolite, while [3]H-6-keto-PGF1alpha was only minimally metabolized. However, on passage through isolated perfused rat lungs, neither [3]H-PGI2 nor [3]H-6-keto-PGF1alpha 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 ot the structure-activity requirements necessary for pulmonary transport and subsequent metabolism.     

Histamine releases PGI2 from human pulmonary artery

Histamine caused a triphasic response of human pulmonary artery strips in vitro, consisting of a small initial contraction followed by pronounced relaxation preceding a second contractile response. These characteristics were not seen with other contractile stimuli including 5-hydroxytryptamine, leukotriene D4, and KCl. The relaxant component of this response was ablated by removal of endothelium from the vascular strips or by pretreatment of the tissue with 1 microM indomethacin. Measurement of the PGI2 degradation product 6-keto-PGF1 alpha in supernatants from histamine-challenged tissues confirmed the synthesis of PGI2. Supernatants from unstimulated or leukotriene-challenged tissues contained no detectable amounts of 6-keto-PGF1 alpha. The histamine H1 antagonist diphenydramine inhibited both the contractile and relaxant responses to histamine whereas the H2 antagonist cimetidine affected neither component. The released PGI2 significantly altered the dose-response curve to histamine without inhibiting the maximal contractile responses. We conclude that histamine induces PGI2 formation from pulmonary arterial endothelium via an H1 receptor.     

Effects of nitrogen dioxide exposure on the contents of prostaglandins and thromboxane B2 in broncho alveolar lavage

Effects of 10 ppm nitrogen dioxide (NO2) exposure on the contents of prostaglandins (PGs) and thromboxane (TX) B2 in bronchoalveolar 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-PGF1 alpha (38.0 +/- 6.4 ng) greater than TXB2 (11.8 +/- 4.0 ng) greater than PGF2 alpha (5.7 +/- 1.6 ng) much greater than 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-PGF1 alpha by about 35% throughout the exposure. The level of TXB2 was higher in the day 5 exposure group (155%). The contents of PGF2 alpha 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 PGF2 alpha and PGE decreased on day 7 and 14. 6-keto-PGF1 alpha 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-PGF1 alpha, a major prostanoid in the BAL and the increase in TXB2 may correlate with broncho constriction by NO2 exposure.     

Cyclooxygenase inhibition with acetylsalicylic acid unmasks a role for prostacyclin in erythropoietin-induced hypertension in uremic rats

We previously reported that thromboxane (TX)A2 synthesis and receptor blockade prevented recombinant human erythropoietin (rhEPO)-induced hypertension in chronic renal failure rats. The present study was designed to investigate the effect of a cyclooxygenase inhibitor, acetylsalicylic acid (ASA), on blood pressure, renal function, and the concentration of eicosano?ds and endothelin-1 (ET-1) in vascular and renal tissues of rhEPO-treated or rhEPO-untreated uremic rats. Renal failure was induced by a 2-stage 5/6 renal mass ablation. Rats were divided into 4 groups: vehicle, rhEPO (100 U/kg, s.c., 3 times per week), ASA (100 mg x kg(-1) x day(-1), and rhEPO + ASA; all animals were administered drugs for 3 weeks. The TXA2- and prostacyclin (PGI2)-stable metabolites (TXB2 and 6-keto-PGF1alpha, respectively), as well as ET-1, were measured in renal cortex and either the thoracic aorta or mesenteric arterial bed. The uremic rats developed anemia, uremia, and hypertension. They also exhibited a significant increase in vascular and renal TXB2 (p < 0.01) and 6-keto-PGF1alpha (p < 0.01) concentrations. rhEPO therapy corrected the anemia but aggravated hypertension (p < 0.05). TXB2 and ET-1 tissue levels further increased (p < 0.05) whereas 6-keto-PGF1alpha was unchanged in rhEPO-treated rats compared with uremic rats receiving the vehicle. ASA therapy did not prevent the increase in systolic blood pressure nor the progression of renal disease in rhEPO-treated or rhEPO-untreated uremic rats, but suppressed both TXB2 and 6-keto-PGF1alpha tissue concentrations (p < 0.05). ASA had no effect on vascular and renal ET-1 levels. Cyclooxygenase inhibition had no effect on rhEPO-induced hypertension owing, in part, to simultaneous inhibition of both TXA2 and its vasodilatory counterpart PGI2 synthesis, whereas the vascular ET-1 overproduction was maintained. These results stress the importance of preserving PGI2 production when treating rhEPO-induced hypertension under uremic conditions.     

Monitoring of the thromboxane A2/prostacyclin ratio in the urine of patients with retinal vascular occlusion through the low-dose-aspirin therapy using the gas chromatography/selected ion monitoring method

We determined the levels of the stable urinary metabolites of thromboxane A2 and prostacyclin, 11-dehydro-thromboxane B2 (11-dehydro-TXB2) and 2,3-dinor-6-keto-prostaglandin F1alpha (2,3-dinor-6-keto-PGF1alpha) in patients with retinal vascular occlusion (RVO) to elucidate the change of the thromboxane A2/prostacyclin (TX/PGI) ratio with this disease and the effect of low-dose-aspirin therapy. 11-Dehydro-TXB2 and 2,3-dinor-6-keto-PGF1alpha were converted to 1-methyl ester-propylamide-9,12,15-tris-dimethylisopropylsilyl ether derivative and 1-methyl ester-6-methoxime-9,12,15-tris-dimethylisopropylsilyl ether derivative, respectively, and applied to a gas chromatography/selected ion monitoring. The average level of 11-dehydro-TXB2 in 30 patients with RVO was 1038 +/- 958 pg/mg creatinine. It was significantly higher than that of 27 healthy volunteers, which was 616 +/- 294 pg/mg creatinine (p < 0.05 with unpaired t-test). However, 2,3-dinor-6-keto-PGF1alpha levels were not significantly different between these two groups. The average ratio of TX/PGI in the RVO patients was 32 +/- 26 and it was significantly higher than that of healthy volunteers, 17 +/- 10 (p < 0.01). Patients with central retinal artery occlusion or branch retinal artery occlusion showed greatly high 11-dehydro-TXB2 levels and TX/PGI ratios, although the number of patients was limited in the current study. After the administration of low-dose aspirin (40 mg/day) for about 1 month, the TX/PGI ratio decreased to around the normal level. Following the levels for up to 10 months, they also remained at the normal level. These observations suggested that the 11-dehydro-TXB2 levels and the TX/PGI ratio reflect the pathological conditions of RVO and are useful markers of the treatment.     

Pulmonary prostacyclin production with increased flow and sympathetic stimulation

We evaluated the effects of an abrupt increase in flow and of a subsequent sympathetic nerve stimulation on the pulmonary production of prostacyclin (PGI2) and thromboxane A2 (TXA2) in canine isolated left lower lobes perfused in situ with pulsatile flow. When flow was abruptly increased from 50 +/- 3 to 288 +/- 2 ml/min, mean pulmonary arterial pressure (Ppa) increased by 15 +/- 2 Torr and then declined by 2.4 Torr over the next 5 min. This secondary decrease in Ppa was associated with a significant 0.26 +/- 0.11 ng/ml increase in the pulmonary venous concentration of the stable PGI2 hydrolysis product 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) as determined by radioimmunoassay. Stimulation of the left stellate ganglion usually resulted in an increase in Ppa which peaked at 1.1 +/- 0.6 Torr above its prestimulus level and then declined over the next 5 min. Associated with this decline was a 0.24 +/- 0.11 ng/ml increase in 6-keto-PGF1 alpha at 1 min. We suggest that the decline in Ppa is due to the synthesis and release of PGI2 by the endothelial cells in response to an increase in perfusion pressure.     

Correlation between dysmenorrheic severity and prostaglandin production in women with endometriosis.

The role of prostaglandins (PGs) in dysmenorrhea of endometriosis is poorly understood. The relationship between dysmenorrheic severity and prostaglandin production was investigated in endometriosis. Slices of normal myometrium, adenomyosis, normal ovary and endometrial cyst were incubated. 6-Keto-PGF1 alpha (a metabolite of PGI2), TXB2 (a metabolite of TXA2), PGF2 alpha, and PGE2 concentrations of the incubation medium were measured by RIA. The results showed that 6-keto-PGF1 alpha production in adenomyosis and endometrial cyst were significantly higher than those in normal myometrium and ovary. A direct relationship between the degree of dysmenorrheic severity and PGs production in tissue in endometriosis was observed.