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.     

Patterns of prostaglandin synthesis and degradation in isolated superficial and proliferative colonic epithelial cells compared to residual colon

Prostaglandin (PG) synthesis and degradation were examined in different regions (epithelial versus non-epithelial structures) of the rat distal colon by both HPLC analysis of [14C] arachidonate (AA) metabolites and by specific radioimmunoassays. Intact isolated colonic epithelial cells synthesized mainly PGF2 alpha and TXA2, as monitored from the formation of its stable degradation product TXB2 (PGF2 alpha greater than TXB2 greater than 6-keto-PGF1 alpha, the stable degradation product of PGI2 = PGD2 = PGE2 = 13,14-dihydro-15-keto-PGF2 alpha). The profile of PG products of isolated surface epithelial cells was identical to that of proliferative epithelial cells. However, generation of PGs by surface epithelium was 2 to 3-fold higher than by proliferative cells both basally and in the presence of a maximal stimulating concentration (0.1 mM) of AA. The latter implied a greater synthetic capacity of surface epithelium, rather than differences due to endogenous AA availability. The major sites of PG synthesis in colon clearly resided in submucosal structures; the residual colon devoid of epithelial cells accounted for at least 99% of the total PGs produced by intact distal colon. The profile of AA metabolites formed by submucosal structures also differed markedly from that of the epithelium. The dominant submucosal product was PGE2. PGE2 and its degradation product 13,14-dihydro-15-keto-PGE2 accounted for 63% of the PG products formed by submucosal structures (PGE2 much greater than PGD2 greater than 13,14-dihydro-15-keto-PGE2 greater than PGF2 alpha = TXB2 = 6-keto-PGF1 alpha greater than 13,14-dihydro-15-keto-PGF2 alpha). By contrast, epithelial cells, and particularly surface epithelium, contributed disproportionately to the PG degradative capacity of colon, as assessed from the metabolism of either PGE2 or PGF2 alpha. When expressed as a percentage, epithelial cells accounted for 71% of total colonic PGE2 degradative capacity but only 23% of total colonic protein. Approximately 15% of [3H] PGE2 added to the serosal side of everted colonic loops crossed to the mucosal side intact. Thus, at least a portion of the PGE2 formed in the submucosa reaches, and thereby can potentially influence functions of the epithelium.     

Altered myocardial prostaglandin synthesis in spontaneously diabetic rats

Patients with diabetes mellitus have an increased susceptibility to heart disease. The exact mechanism for this phenomenon is unclear. Abnormalities in prostaglandin (PG) production have been suggested as a possible cause. In this connection, we examined the PG synthetic capacity of cardiac microsomes from spontaneously diabetic rats. Cardiac microsomes from diabetic and control rats produced varying amounts of 6-keto-PGF1 alpha (stable degradation product of PGI2), PGE2, PGD2, PGF2 alpha, and TXB2 (stable breakdown product of TXA2). In both instances the production of 6-keto-PGF1 alpha predominated, however, microsomes from diabetic rats showed markedly greater conversion of arachidonic acid to all the PG products, especially 6-keto-PGF1 alpha. When PGF2 alpha metabolism was detected between diabetic and control heart preparations. These results show an enhanced cyclooxygenase activity in diabetic rat hearts without any change in prostaglandin dehydrogenase activity. Such a change may promote some of the cardiac alterations seen in diabetic mellitus.     

Thymic hormones and prostaglandins II. Synergistic effect on mouse spontaneous rosette forming cells

Prostaglandins (PGs) have been assummed to play a role in the biological activity of thymic hormones (TH). Indeed, it has been shown that type E-PGs are able to mimic the action of several TH. Moreover, indomethacin interferes in the rosette assay, which still represents the most commonly used bioassay for the evaluation of TH and, in particular thymulin levels, in biological fluids. Previously, our attempt to modulate PG production by different TH showed that none of the TH tested affect PGE2, 6-keto-PGF1α, PGF2α and TXB2 production by spleen cells from control and thymectomized (Tx) mice, while indomethacin was able to inhibit the spontaneous PG production. Here, we investigated a possible role for each endogenously produced PG in the experimental conditions of the rosette assay, in order to define : 1) whether or not there was a specificity of action of a given PG ; and 2) to analyze the pattern of action between thymulin and the endogenously produced PGs. We demostrated that PE2 and 6-keto-PGF1α are the PGs which are physiologically involved in the rosette assay, according to their levels of endogeneous production, and that they are able to synergize with thymulin. This synergy was demonstrated in two ways: 1) by adding anti-PGE2 and anti-6-keto PGF1α-antibodies, which prevent part of the thymulin effect, or 2) by simultaneous addition of PG and thymulin, at concentrations far lower than those which correspond to their thymulin-like effect. Moreover, PGE2 addition, at concentration close to that found to be endogenously produced, partially reversed the indomethacin-induced effect in the rosette assay. In conclusion, if PGs do not act as mediators of thymulin, they are able to synergize in one of its biological action.     

Synthesis of 6-keto-PGF1α by ram seminal vesicle microsomes

At low substrate/enzyme ratios, and in the absence of reduced glutathione (GSH), the major prostaglandin (PG) biosynthesised by the ram seminal vesicle cyclo-oxygenase from arachidonic acid was 6-keto-PGF1α. The addition of nanomolar amounts of reduced GSH suppressed biosynthesis of this product and stimulated the formation of PGE2; 1-epinephrine enhanced the conversion of the substrate but had not effect on the type of product formed. 15-Hydroperoxy arachidonic acid selectively inhibited formation of 6-keto-PGF1α (IC50 100 μM) but blocked synthesis of all cyclooxygenase products at concentations greater than 1 mM. At substrate concentrations of 30 μM or greater, synthesis of 6-keto-PGF1α was inhibited and PGE2 and PGF2α were the main products formed.     

Prostanoid synthesis by vascular slices and cultured vascular cells of piglet aorta

Biosynthesis of prostanoids was studies in vascular slices of human umbilical arteries, piglet aorta and vena cava as well as in cultured vascular cells of piglet aorta. After preincubation with radioactive labeled arachidonic acid, prostanoids in the incubation media of slices or cultured cells were measured by radioimmunoassay or by radioactivity determination of labeled compounds following separation on reserved-phase high performance liquid chromatography. In all vascular slices 6-keto-PGF1α was the main prostanoid found, followed by PGE2. Thromboxane B2 and PGF2α were also formed, but only in trace amounts. In cultured cells taken from the three layers of the vascular wall, the prostanoid profiles differed markedly from those obtained from vascular slices. Each cell strain showed a specific prostanoid pattern. Endothelial cells synthesized predominantly 6-keto-PGF1α and PGF2α. In smooth muscle cells no 6-keto-PGF1α could be detected; here the predominant prostanoid was PGE2. PGF2α was formed in smaller quantities. Fibroblasts synthesized all prostanoids (PGE2, PGF2α, TXB2, 6-keto-PGF1α), PGE2 and PGF2α being the major products. In vascular slices and in cultured endothelial cells, the predominant prostacyclin derivative detected was 6-keto-PGF1α; the enzymatic PGI2-metabolite, 6,15-diketo-PGF1α, could be detected only in piglet vena cava slices in small amounts.     

Comparison of plasma prostanoid levels in the human cord artery in normal and fetal distressed deliveries

Prostaglandin E2 (PGE2), thromboxane B2 (TXB2; as a stable metabolite of TXA2), prostaglandin F2 alpha (PGF2 alpha) and 6-keto-PGF1 alpha (as a stable end product of prostacyclin) have been measured by using specific radioimmunoassay in the plasma of the cord artery immediately after delivery before the cord was clamped. Plasma prostanoid concentrations in normal deliveries (n = 8, as controls) were 24.8 +/- 2.6 (PGE2), 246.8 +/- 37.0 (TXB2), 122.2 +/- 13.3 (PGF2 alpha) and 82.1 +/- 7.7 (6-keto-PGF1 alpha) respectively (pg/ml, mean +/- s.e). On the other hand, in fetal distressed deliveries showing continuous bradycardia (n = 6), they increased significantly to 275.4 +/- 20.1 (PGE2), 948.6 +/- 102.5 (TXB2), 218.0 +/- 21.4 (PGF2 alpha) and 1498.6 +/- 298.4 (6-keto-PGF1 alpha) respectively (pg/ml, mean +/- s.e, p less than 0.005). However, both PGF2 alpha/PGE2 and TXB2/6-keto-PGF1 alpha ratios declined significantly from 4.70 +/- 0.33 to 0.68 +/- 0.05 and from 3.07 +/- 0.37 to 0.68 +/- 0.12 respectively (mean +/- s.e, p less than 0.005) in the fetal distressed group compared with those of the controls. From these results, it may be concluded that the cord artery, which is known as the patent source for the production of PGE2 and prostacyclin, did exert a sufficiently strong reaction to overcome the undesirable haemodynamic changes to maintain the fetal well-being in utero.     

Calcium-dependent prostaglandin biosynthesis by lipopolysaccharide-stimulated rat Kupffer cells.

Isolated rat Kupffer cells produced and released prostaglandin (PG) E2, 6-keto-PGF1 alpha, and thromboxane B2 (TXB2) in response to lipopolysaccharide (LPS) stimulation. This elevation of PGE2, 6-keto-PGF1 alpha and TXB2 in the medium was not observed when cells were cultured in the absence of extracellular calcium or in the presence of an extracellular calcium chelator, EGTA. An intracellular calcium antagonist, TMB-8, also suppressed the production of PGE2, 6-keto-PGF1 alpha and TXB2 in a concentration-dependent manner. The intra-cellular calcium concentration of Kupffer cells elevated early after the addition of LPS determined by the use of fura-2 and a fluorescence microscopy. Moreover, calmodulin inhibitors, W-7 and W-13, apparently inhibited the production of PGF2, 6-keto-PGF1 alpha and TXB2. All these results suggest that LPS-induced PG production by stimulated rat Kupffer cells may be regulated by a calcium-calmodulin pathway.     

Effect of prostaglandins against alloxan-induced diabetes mellitus

Previously, we observed that alloxan-induced in vitro cytotoxicity and apoptosis in an insulin secreting rat insulinoma, RIN, cells was prevented by prior exposure to prostaglandin (PG) E(1), PGE(2), PGI(2), PGF(1)(alpha), and PGF(3)(alpha) (P<0.05 compared to alloxan), whereas thromboxane B(2) (TXB(2)) and 6-keto-PGF(1)(alpha) were ineffective. In an extension of these studies, we now report that prior intraperitoneal administration of PGE(1), PGE(2), PGF(1)(alpha), and PGF(3)(alpha) prevented alloxan-induced diabetes mellitus in male Wistar rats, whereas PGI(2), TXB(2), and 6-keto PGF(1)(alpha) were not that effective. PGE(1), PGE(2), PGF(1)(alpha), and PGF(3)(alpha) not only attenuated chemical-induced diabetes mellitus but also restored the antioxidant status to normal range in red blood cells and pancreas. These results suggest that PGE(1), PGE(2), PGF(1)(alpha), and PGF(3)(alpha) can abrogate chemically induced diabetes mellitus in experimental animals and attenuate the oxidant stress that occurs in diabetes mellitus.     

Effects of oestradiol, progesterone, hydrocortisone and oxytocin on prostaglandin output from the guinea-pig endometrium maintained in tissue culture

The effects of oestradiol, oxytocin, progesterone and hydrocortisone in vitro on prostaglandin (PG) output from guinea-pig endometrium, removed on days 7 and 15 of the oestrous cycle and maintained in tissue culture for 3 days, have been investigated. Oestradiol (3.7 to 3700 nM) and oxytocin (2 to 200 pM) did not stimulate endometrial PGF2 alpha output, thus not confirming the findings of a previous report (Leaver & Seawright, 1982), nor did they stimulate the outputs of PGE2 and 6-keto-PGF1 alpha. In fact, oestradiol (3700 nM) inhibited the outputs of PGF2 alpha, PGE2 and, to a lesser extent, 6-keto-PGF1 alpha. Progesterone (3.2 to 3200 nM) inhibited the outputs of PGF2 alpha and PGE2; hydrocortisone (2.8 to 2800 nM) had no effect on endometrial PG output. These findings indicate that the inhibitory effect of progesterone on endometrial PG synthesis and release in the guinea-pig is not due to progesterone having a glucocorticoid-like action. Furthermore, progesterone had no effect on 6-keto-PGF1 alpha output, suggesting that the mechanisms controlling endometrial PGI2 synthesis (as reflected by measuring 6-keto-PGF1 alpha) are different from those controlling endometrial PGF2 alpha and PGE2 synthesis.     

Effects of experimental diabetes on spontaneous contractions, on the output of prostaglandins and on the metabolism of labelled arachidonic acid, in uteri isolated from ovariectomized rats. Influences of estradiol

Spontaneous changes in isometric developed tension (IDT) as a function of time after isolation (contractile constancy) in uteri from control-castrated and castrated chronic streptozotocin-diabetic rats, were explored. The effects of injecting 17-beta estradiol (Eo) were also studied. No differences in the minor changes of contractile constancy, between control and diabetic preparations, during a period of 60 min, were detected, whereas uteri from non-diabetic Eo injected animals (0.5 + 1.0 ug, prior to sacrifice), exhibited a profound reduction of IDT, significantly greater than in tissues obtained from Eo injected-diabetic rats. Moreover, basal generation and outputs into the suspending solution of prostaglandins (PGs) E1, E2 and F2 alpha, were explored in the same groups, at 60 min following tissue isolation. The basal outputs of these three PGs were similar in castrated control rats, but preparations from castrated-diabetics released significantly more PGE1. The administration of Eo to castrated-diabetics, failed to alter the releases of the three PGs explored. In addition, the metabolism of labelled arachidonic acid (AA) into different prostanoids (6-keto-PGF1, PGF2, PGE2 and thromboxane B2-TXB2), was also investigated. The non-diabetic spayed rat uterus converted AA into these four prostanoids, the transformation into 6-keto-PGF1 alpha (as an index of PGI2 formation) being the most prominent. In preparations from diabetic rats the formation) being the most prominent. In preparations from diabetic rats the formation of 6-keto-PGF1 alpha, PGF2 alpha and PGE2, was significantly smaller than in controls, whereas a greater % of TXB2 formation (as an index of TXA2), was detected. On the other hand uterine preparations from non-diabetic spayed rats injected with Eo formed less 6-keto-PGF1 alpha and PGE2 and similar amounts of PGF2 alpha or of TXB2 from AA, than Eo injected controls, whereas uteri from castrated diabetic animals injected with Eo, formed a similar % of 6-keto-PGF1 alpha, PGF2 alpha and PGE2 from AA, than tissue preparations from non-estrogenized controls. However, the enhanced transformation of the labelled fatty acid precursor (AA) into TXB2 in the diabetic group, was significantly reduced by the steroid. The role of the augmented generation and release of PGE1 in uteri from diabetic rats is discussed in terms of precedents indicating the relevance of PGs type E supporting rat uterine motility. In addition the influence of Eo is attractive, because its reducing effect on TX production, in diabetes, a disease known to be accompanied by enhanced synthesis of vasoconstrictor and platelet aggregation TXA2, and by frequent obstructive circulat     

Production of prostacyclin, 6-keto-PGF1α and thromboxane B2 by incubated samples of umbilical vessels: A comparison of methods for expressing the reults on dry weight, wet weight, protein or DNA bases

The production of PG12 (determined by abioassay), and of 6-keto-PGF1α and TXB2 (determined by radioummunoassay) by samples of human umbilical vessels have been measured. The results have been calculated on four bases: dry weigt, wet weight, protein and DNA.There was a higher production of PG12 and 6-keto-PGF1α 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-PGF1α: TXB2 production was about 100 for the samples of veins and about a40 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.     

The effect of estradiol-17β and actinomycin D on the release of PGF and PGE from separated cells of human endometrium

Estradiol-17β selestively stimulated the release of PGF from separated glandular but not stromal cells of human secretory endometrium (p<0.025) but had no effect on PGF release from either type of cells obtained from proliferative endometrium. PGE release was not affected by estradiol-17β. Actinomycin D did not antagonise the effect of estradiol-17β on PGF release from secretory, glandular cells. Basal release of PGF from these cells was stimulated by actinomycin D alone (100 ng/ml) (p<0.025) and PGE release stimulated in the presence of estradiol-17β. Actinomycin D had no effect on PGF or PGE release from proliferative endometrium. These findings suggest that estradiol-17β stimulates PGF release by a mechanism that does not affect PGE release and which is not dependent on the synthesis of new protein. The basal release of PGF and PGE by glandular cells of secretory endometrium in vitro is regulated by protein/proteins which reduce PG release.     

Effect of dipyridamole on prostanoid production in rat isolated atria.

The effect of 0.01 microM dipyridamole on prostanoid production was studied in atria from normal, acute diabetic and insulin-treated diabetic rats. Diabetes was induced by i.v. administration of 65 mg/kg of streptozotocin (STZ) and the rats were killed 5 days later. Atria were incubated during 60 min in Krebs solution. The prostanoids 6-keto-prostaglandin (PG) F1alpha (6-keto-PGF1alpha) and thromboxane (TX) B2, stable metabolites of prostacyclin and TXA2, respectively, as well as PGE2 were measured by reversed phase high-performance liquid chromatography-UV. In diabetic atria, 6-keto-PGF1alpha production was reduced by 50% whereas TXB2 release was increased two-fold compared to the controls, with a significant decrease in the 6-keto-PGF1alpha/TXB2 ratio. The preincubation with 0.01 microM dipyridamole for 30 min increased 6-keto-PGF1alpha production in control, diabetic and insulin-treated diabetic atria whereas TXB2 release was not modified. This effects provoked an significant increase in the 6-keto-PGF1alpha/TXB2 ratio. In conclusion, STZ diabetes reduces the 6-keto-PGF1alpha/TXB2 ratio impairing the functional status of the atria. Dipyridamole increased this ratio in atria from diabetic and insulin-treated diabetic rats, thus opposing the effects of STZ diabetes. This fact suggests the possibility of a participation of the drug in pathologies characterized by an imbalance in the production of vasodilator and vasoconstrictor prostanoids.     

Prostaglandins and premenstrual syndrome.

We examined plasma PGF2 alpha, PGE, PGE2, TXB2 and 6-keto-PGF1 alpha at intervals throughout 3 menstrual cycles in 20 patients with PMS. Similar measurements throughout 1 menstrual cycle were made in 12 age-matched control women. The plasma concentration of PGF2 alpha in the late luteal phase was significantly lower in patients with PMS compared with that in the control subjects. The plasma concentrations of PGE in the middle follicular phase and middle luteal phase, PGE2 alpha in the middle follicular phase and TXB2 in the middle and late luteal phase were significantly higher in 20 patients compared with the values in the controls. A disturbance of PG metabolism may contribute to the etiology of PMS.     

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.     

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.     

High glucose levels modulate eicosanoid production in uterine and placental tissue from non-insulin-dependent diabetic rats during late pregnancy

Severe uterine and placental disturbances have been described in diabetes pathology. The relative severity of these changes appears to correlate with high glucose levels in the plasma and incubating environment. In order to characterize changes in eicosanoid production we compared uterine and placental arachidonic acid conversion from control and non-insulin-dependent diabetes mellitus (NIDDM) rats on day 21 of pregnancy, into different prostanoids, namely PGE2, PGF22alpha, TXB2 (indicating the production of TXA2) and 6-keto-PGF1 (indicating the generation of PGI2). PGE2, PGF2alpha and TXB2 production was higher and 6-keto-PGF1alpha was similar in diabetic compared to control uteri. PLA2 activity was found diminished in the NIDDM uteri in comparison to control. A role for PLA2 diminution as a protective mechanism to avoid prostaglandin overproduction in uterine tissue from NIDDM rats is discussed. Placental tissues showed an increment in TXB2 generation and a decrease in 6-keto PGF1alpha level in diabetic rats when compared to control animals. Moreover, when control uterine tissue was incubated in the presence of elevated glucose concentrations (22 mM), similar generation of 6-keto PGF1alpha and elevated production of PGE2, PGF2alpha and TXB2 were found when compared to those incubated with glucose 11 mM. Placental TXB2 production was higher and 6-keto PGF1alpha was lower when control tissues were incubated in the presence of high glucose concentrations. However, high glucose was unable to modify uterine or placental prostanoid production in diabetic rats. We conclude that elevated glucose levels induced an abnormal prostanoid profile in control uteri and placenta, similar to those observed in non-insulin-dependent diabetic tissues.     

Failure of acute hypoxia to alter pulmonary prostaglandin metabolism in dogs

We studied the effects of acute hypoxia (Fi02=0.09–0.11, 20 min,.) on transpulmonary plasma prostaglandin (PG) concentrations in ten anaesthetized, paralyzed, artificially ventilated dogs. Concentrations of 6-keto-PGF1α, TxB2, PGE2, PGF2α, and 13, 13-dihydro-15-keto-PGF2α were measured from the pulmonary artery and abdominal aorta using radioimmunoassay. In an additional six dogs, the effects of arachidonic acid (AA) infusions (100 mg/kg/min) during normoxia and acute hypoxia were determined. Compared to normoxic conditions, acute hypoxia increased pulmonary artery pressure (p<0.0), decreased both the arterial oxygen tension (Pa02) and the alveolar-to-arterial oxygen tension gradient (A-aD02) (p <0.05), but did not affect transpulmonary plasma PG concentrations. AA infusions significantly (p <0.05) increased 6-keto-PGF1α independent of Fi02. Acute hypoxia failed to elicit a pulmonary pressor response in the AA-treated animals although Pa02 and A-aD02 decreased (p<0.5). These data in healthy dogs suggest that (1) acute hypoxia does not alter net pulmonary PG metabolism, (2) prostacyclin synthesis is stimulated by increased plasma AA concentrations and (3) this effect may block normal pressor responses to hypoxic stimuli.     

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.