Reevaluation of circulating prostacyclin and thromboxane in diabetes

Although several investigators have attempted to measure the plasma levels of prostacyclin (PGI₂) and thromboxane A₂ (TXA₂) in diabetes and normal subjects, their results have been controversial. In this study, we measured plasma PGI₂ and TXA₂ levels in diabetic patients and normal subjects. The plasma PGI₂ and TXA₂ were determined by RIA as 6-keto-PGF_1a and TXB₂, respectively. The plasma levels of 6-keto-PGF_1a were significantly reduced in diabetics with microangiopathy (52.5 ± 18.9 pg/ml, mean ± SE, p<0.05) compared with those of normal subjects. Diabetics as a whole also showed lower levels of 6-keto-PGF_1a than normal subjects (57.8 ± 26.1 vs. 70.2 ± 20.7 pg/ml), though this was not significant statistically. The plasma 6-keto-PGF_1a levels did not significantly correlate with either age of the patients or duration of diabetes in diabetics. Interestingly, however, hemoglobin Alc significantly correlated inversely with 6-keto-PGF_1a levels in diabetics without microangiopathy (r=−0.60, p<0.05). The plasma levels of TXB₂ in diabetics were significantly higher than those of normal subjects (155.2 ± 69.5 vs. 108.0 ± 30.0 pg/ml, p<0.05). These data suggest that an imbalance of circulating PGI₂ and TXA₂ may contribute to the development of diabetic microangiopathy.     

Prostanoids and hemodynamics in man before and during cardiopulmonary bypass

The plasma concentration of 6-keto-PGF_1α, the stable degradation product of prostacyclin, was similar in the radial and pulmonary arteries and in the coronary sinus before and after the induction of the anesthesia in patients undergoing coronary artery bypass surgery. After the beginning of the mechanical ventilation and anesthesia the pulmonary vascular resistance decreased although no changes were detected in the plasma levels of 6-keto-PGF_1α or TXB₂. During the prebypass period after the sternotomy and cannulation of the large vessels the plasma level of 6-keto-PGF_1α was increased similarly in the radial and pulmonary arteries and even more in the coronary sinus. During the cardiopulmonary bypass the concentration of 6-keto-PGF_1α remained at the increased level as compared to the values before the anesthesia. This indicates that pulmonary circulation is perhaps not the main source of prostacyclin in man. The plasma level of TXB₂ was increased during the prebypass period significantly only in the coronary sinus, but during the bypass also in the radial artery. The concentration ratio of 6-keto-PGF_1α/TXB₂ was increased significantly during the prebypass period in the radial and pulmonary arteries. At the same time the pulmonary vascular resistance was, however, returned to the preanesthesia level and was thus not decreased. The vascular resistance in the systemic circulation was increased during the prebypass period. The plasma level of 6-keto-PGF_1α or TXB₂ in the radial and pulmonary arteries did not correlate significantly with the total vascular resistance in the systemic and pulmonary circulation, respectively. The vascular resistance in the coronary circulation did not correlate significantly with TXB₂ level in the radial artery or coronary sinus. There was, however, a slight positive correlation between the blood flow and the concentration of TXB₂ in the coronary sinus (r=0.76, P < 0.01). Coronary sinus flow did, however, not correlate with the plasma level of 6-keto-PGF_1α in the radial artery or coronary sinus. These results indicate that the detected plasma concentrations of prostacyclin and thromboxane A₂ have no significant effects on the total vascular resistance in vivo.     

Hyperglycemia promotes elevated generation of TXA2 in isolated rat uteri

The relationship between high glucose concentrations and arachidonic acid metabolism in uterine tissue from control and diabetic ovariectomized rats was evaluated. Uterine tissue from diabetic rats produced amounts of PGE₂ and PGF_2α similar to controls, while a lower production of 6-keto-PGF_1α (indicating the production of prostacyclin) and a higher production of TXB₂ (indicating the generation of TXA₂) was found in the diabetic group. A group of diabetic rats was treated with phlorizin to diminish plasma glucose levels. Phlorizin treatment did not alter production of PGE₂, PGF_2α, and 6-keto-PGF_1α in the diabetic group. A diminished production of TXB₂ was found in the treated diabetic uteri when compared to the non-treated diabetic group. Moreover, a positive correlation between plasma glucose levels and uterine TXB₂ generation was observed. When control uterine tissue was exposed in vitro to high concentrations of glucose (22 mM) and compared to control tissue incubated in the presence of glucose 11 mM alterations in the generation of PGE₂, PGF_2α, and 6-keto-PGF_1α were not found, but a higher production of TXB₂ was observed and values were similar to those obtained in the diabetic tissue. Alteration in the production of the prostanoids evaluated were not observed when diabetic tissue was incubated in the presence of high concentrations of glucose. These results provide evidence of a direct relationship between plasma glucose levels and uterine production of TXA₂.     

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 continously perfused human umbilical vein and supernatants from umbilical vein rings for TXB₂ and 6-keto-PGF_1α measurements (stable metabolites of TXA₂ and PGI₂, respectively). TXB₂ and 6-keto-PGF_1α were identified in all samples. 6-keto-PGF_1α to TXB₂ ratio was higher in intact vein effluents than in the venous ring supernatants (112:1 and 28:1, respectively, P<0.01). Arachidonate stimulation increased 6-keto-PGF_1α 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-PGF_1α. This caused 6-keto-PGF_1α to TXB₂ ratio to decline (p<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-PGF_1α and TXB₂) during stimulation with vasoactive autocoids was registered in human umbilical arteries perfused . Responses were registered within 3–4 minutes after addition of the subtances. Both angiostensin 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 PGF_2α stimulated the PGI₂ formation. The TXA₂ mimetic U46619, increased PGI₂ production, whereas PGI₂ slighlty increased the formation of TXA₂. All responses were found to be completely inhibited by indomethacin.     

The concentration of 6-keto-PGF1α and TXB2 in plasma samples from patients with benign and malignant tumours of the breast

Peripheral plasma concentrations of 6-keto-PGF_1α and TXB₂ were measured in patients with benign and malignant tumours of the breast, in patients with nongynecological disease,a nd in healthy female controls. The values were significantly higher in female patients with maligants tumours of the breast than in healthy controls (146 ± 28 vs 13 ± 2.5 pg/ml for 6-keto-PGF_1α p<0.01 and 78 ± 17 vs 11 ± 2 pg/ml for TXB₂, p<0.01). Benign tumours of the breast were also associated with significantly raised plasma levels of 6-keto-PGF_1α and TXB₂ compared to normal controls (52 ± 5 vs 13 ± 2.5 pg/ml for 6-keto-PGF_1α, p < 0.01 and 26 ± 5 vs 11 ± 2 pg/ml for TXB₂, p < 0.05). The high levels of 6-keto-PGF_1α and TXB₂ were not found to be correlated with clinical and histopathological data. The surgical removal of the primary tumour has apparently no effect on the plasma concentration of 6-keto-PGF_1α and TXB₂ over a follow-up period of 9 days after operation. The lack of alterations in the ratio of TXB₂: 6-keto-PGF_1α in the cancer patients and other subjects studied before and after surgery is indicative of the regulatory power of metabolic systems to preserve the homeostatic balance.     

Modulation of the platelet thromboxane A2 and aortic prostacyclin synthesis by dietary selenium and vitamin E

Vitamin E and selenium (Se) interact synergistically as an important antioxidant defense mechanism. Se, an essential component of glutathione peroxidase (GSH-Px) and vitamin E decompose fatty acid hydroperoxides and hydrogen peroxides generated by free radical reactions. Vitamin E and GSH-Px may modulate arachidonic acid metabolism and the activity of cyclooxygenase enzymes by affecting peroxide concentration. The balance between arterial wall prostacyclin (PGI₂) production and platelet thromboxane (TX)A₂ directly influences platelet activity. In order to elucidate the differential role of dietary vitamin E and Se in aortic PGI₂ and platelet TXA₂ synthesis, 1-mo-old F344 rats were fed semipurified diets containing different levels of vitamin E (0, 30, 200 ppm) and Se (0, 0.1, 0.2 ppm) for 2 mo. Thromboxane B₂ (TXB₂) and 6-keto-PGF₁α, were measured by radioimmunoassay (RIA) after incubation of whole blood and aortic rings at 37°C for 10 and 30 min, respectively. Vitamin E deficiency reduced plasma vitamin E to 5–17% of control-fed rats, and supplementation increased it to 53% of the control-fed rats. Se supplementation in vitamin E-supplemented animals increased plasma GSH-Px by 17%, compared to vitamin E-deficient rats. Se and vitamin E supplementation did not have a similar effect on TXB₂ and PGI₂ synthesis. Se deficiency did not alter platelet TXB₂ synthesis, but significantly decreased aortic PGI₂ synthesis. It was necessary to supplement with both antioxidants in order to increase, PGI₂ synthesis. Se and vitamin E deficient groups had a higher TXB₂/PGI₂ ratio (0.17±0.08) compared to Se- and vitamin E-supplemented groups (0.03±0.01). These results confirm previous reports in humans and animals and are in accordance with epidemiological data indicating an inverse relationship between plasma Se and platelet aggregation. Thus, further suggesting that vitamin E and Se may have a specific role in controlling TXA₂ and PGI₂ synthesis.     

Plasma prostaglandin levels and circulating fuel levels in rats with diabetic ketoacidosis: Effects of cyclooxygenase inhibitors and of alpha and beta adrenergic blockade

We studied the effects of two structurally unrelated inhibitors of the fatty acid cyclooxygenase and of alpha and beta adrenergic blockade on the elevated plasma levels of 13,14-dihydro-15-keto-prostaglandin (PG)E₂, 6-keto-PGF_1α and thromboxane(TX)B₂, the stable derivatives of PGE₂, PGI₂ (prostacyclin) and TXA₂, respectively, in rats with streptozotocin-induced diabetic ketoacidosis (DKA). Meclofenamic acid and indomethacin each produced a significant decrease in the elevated plasma levels of 13,14-dihydro-15-keto-PGE₂, 6-keto-PGF_1α and TXB₂. Phentolamine significantly reduced the plasma level of TXB₂ but had no effect on the elevated circulating levels of glucose, free fatty acids, total ketones, 13,14,-dihydro-15-keto-PGE₂ or 6-keto-PGF_1α. Propranolol significantly reduced the elevated circulating levels of glucose, free fatty acids and total ketones but had no effect on the levels of the three prostaglandin derivatives. The ability of meclofenamic acid and indomethacin to reduce the plasma levels of 13,14-dihydro-15-keto-PGE₂, 6-keto-PGF_1α and TXB₂ confirms that the plasma levels of these three derivatives are elevated in rats with DKA. Since abnormalities in the production of PGI₂ and perhaps other cyclooxygenase derivatives may contribute to the pathogenesis of certain important hemodynamic and gastrointestinal features of DKA, cyclooxygenase inhibitors may play a role in the management of selected patients with this disorder. Alpha adrenergic activity is essential for the maintenance of the elevated plasma TXB₂ level in rats with DKA. The fall in the plasma TXB₂ level during alpha adrenergic blockade appears to reflect inhibition of platelet aggregation and platelet TXA₂ production, but other sources of the elevated plasma TXB₂ level in DKA are not excluded. Beta adrenergic activity contributes to the maintenance of elevated circulating levels of glucose, free fatty acids and total ketones in experimental DKA but not to the elevated plasma levels of the prostaglandin derivatives.     

Selective inhibition of thromboxane synthesis partially protected while inhibition of angiotensin II formation did not protect rats against acute renal failure induced with glycerol

Acute renal failure (ARF) was induced in 35 week-old conscious female Wistar rats, by intramuscular (IM) injection of glycerol. Intraperitoneal (IP) injection of imidazole, an inhibitor of thromboxane (TXA₂) synthesis, partially protected the animals against ARF. This protection was accompanied by a significant decrease in renal TXB₂ (the stable chemical metabolite of TXA₂) and a significant increase in renal 6-keto-PGF₁α (the stable chemical metabolite of PGI₂) synthesis. Intraperitoneal injection of captopril (SQ 14225) an angiotensin-converting-enzyme inhibitor, did not protect the animals against ARF. This lack of protection was accompanied by a significant increase in renal TXB₂ and a significant decrease in renal 6-keto-PGF₁α synthesis. The results suggest that: (a) the renin-angiotensin (R-A) system does not play a role, or has only a secondary one in the development of ARF; (b) thromboxane A₂ (the most potent vasoconstrictor and platelet aggregator agent known) is the preponderant agent responsible for the development of this pathological syndrome.     

Formation of prostanoids in human umbilical vessels perfused

Four major prostanoids (6-keto-PGF_1α, PGE₂, PGF_2α and TXB₂) were measured by specific radioimmunoassays in the outputs from human umbilical vessels perfussed . As evaluated by scanning electron microscopy (SEM) only few blood platelets were attached to the vessel wall. After an initial flush with decreasing concentrations of all four prostanoids, a stable stage was reached, lasting for 4–5 hours. During this stage the production could be inhibited by indomethacin and only slightly stimulated with arachidonic acid. The TXA₂ synthetase inhibitor UK 38485 depressed the TXB₂ production, while only slightly affecting the other three prostanoids at very high concentrations. The arteries produced relatively more 6-keto-PGF_1α than did the vein.     

Circulating prostacyclin and thromboxane in patients with graves' disease

We measured plasma levels of PGI₂ as 6-keto-prostaglandin F_la (6-keto-PGFla) and thromboxane A₂ (TXA₂) as thromboxane B₂ (TXB₂) in patients with Graves' disease and in normal subjects. The levels of plasma 6-keto-PGFla were significantly elevated and correlated with those of serum T₄ and T₃, respectively, in hyperthyroid patients with Graves' disease. Significant reduction of 6-keto-PGF_1a levels was observed after antithyroid drug therapy. In contrast, the levels of plasma TXB₂ were significantly lower in untreated patients with Graves disease than in normal subjects. These data suggest that an elevation of plasma 6-keto-PGF_1a may play some additional role in pathophysiology of Graves disease.     

Regulation of microvascular prostacyclin and thromboxane with inhibitors or arachidonic acid metabolism

The levels of the stable degradation products of prostacyclin (PGI₂) and thromboxane A₂ (TXA₂): 6-oxo-prostaglandin F_1α(6-oxo-PGE_1α) and thromboxane B₂ (TXB₂) respectively were determined in the effluent of the rabbit epigastric skin flap after infusion of exogenous arachidonic acid. The blood to the flap passes through the microcirculation and thus the changes in eicosanoid biosynthesis in this part of the vasculature were recorded. The aim was to use inhibitors of arachidonic acid metabolism to increase the PGI₂/TXA₂ ratio. This may be potentially beneficial to ischaemic skin flaps by reducing platelet aggregation associated with damaged microvascular endothelium, overcoming vasospasm and increasing microvascular blood flow. Increased PGI₂/TXA₂ ratios (up to 5-fold) were best achieved using TXA₂ synthetase inhibitors such as dazoxiben hydrochloride. These were significantly more potent than the phosphodiesterase inhibitor dipyridamole, and the lipoxygenase inhibitor Bay g6575. No increase in blood flow was achieved. The cyclooxygenase inhibitor indomethacin did slow the blood flow at high concentrations (above 10⁻⁵ M), and inhibited both PGI₂ and TXA₂ synthesis. Approximately 2-fold higher concentrations of dazoxiben hydrochloride and dipyridamole were required to produce the same TXA₂ synthetase inhibition in the flap microvasculature compared with platelets .     

Effects of Danshensu on Platelet Aggregation and Thrombosis: In Vivo Arteriovenous Shunt and Venous Thrombosis Models in Rats

Danshensu, a type of dihydroxyphenyl lactic acid, is one of the most abundant active phenolic acids in the dried root of Salvia miltiorrhizae (Lamiaceae)—widely used traditional Chinese medicine. The effects of danshensu on platelet aggregation and thrombus formation in rats were examined using various methods. It was found that danshensu significantly reduced thrombus weight in 2 experimental thrombosis models; dose-dependent inhibition of adenosine diphosphate (ADP) and arachidonic acid (AA)-induced platelet aggregation occurred in normal and blood stasis-induced rats; Danshensu also significantly mitigated blood viscosity, plasma viscosity and hematocrit levels. Moreover, danshensu significantly inhibited venous thrombosis-induced expression of cyclooxygenases-2 (COX-2) rather than cyclooxygenases-1(COX-1) in the venous walls, down regulated thromboxane B₂ (TXB₂) and up regulated 6-keto prostaglandin F_1α (6-keto-PGF_1α), normalizing the TXB₂/6-keto-PGF_1α ratio. In addition, danshensu did not induce gastric lesions and even had protective effects on aspirin-induced ulcer formation at doses as high as 60 mg/kg. These findings suggest that the antithrombotic and antiplatelet aggregation effects of danshensu are attributed to its highly selective inhibition of COX-2 and ability to normalize the thromboxane A₂(TXA₂)/prostacyclin(PGI₂) balance. These findings suggest that danshensu have great prospects in antithrombotic and antiplatelet therapy.     

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-PGF_1α 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 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 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.     

Prostacyclin and thromboxane A2 release in isolated rat lungs

The influence of platelets and platelet membranes on the generation of prostacyclin (PGI₂) and thromboxane A₂(TXA₂) by isolated rat lung and porcine aortic endothelial cell, as measured by RIA of their stable end-producs, 6-oxo-PGF_1α and TXB₂ respectively, was studied. After introduction of either aspirin-treated platelets or membranes from aspirin-treated platelets to the perfusate, 1 5-fold increase in the amount of 6-oxo-PGF_1α and TXB₂ in the perfusate was observed. Treatment of the lung with aspirin produced a 50% reduction in the platelet-stimulated release of PGI₂ and TXA₂. Treatment of the lung with the phospholipase inhibitor, mepacrine, significantly reduced the platelet-stimulated release of PGI₂ and TXA₂. Incubation of endothelial cells with untreated platelet membranes did not alter the generation of PGI₂. These results suggest that platelet-stimulated release of PGI₂ and TXA₂ occurs via mechanical stimulation of phospholipase A₂, liberating arachidonic acid.     

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 broncho-alveolar 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-PGF_1α (38.0 ± 6.4 ng) > TXB₂ (11.8 ± 4.0 ng) > PGF_2α (5.7 ± 1.6 ng) 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-PGF_1α by about 35% throughout the exposure. The level of TXB₂ was higher in the day 5 exposure group (155%). The contents of PGF_2α 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 PGF_2α and PGE decreased on day 7 and 14.6-keto-PGF_1α 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-PGF_1α, a major prostanoid in the BAL and the increase in TXB₂ may correlate with broncho constriction by NO₂ exposure.     

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, PGF_2α and the stable metabolites of PGI₂ (6-keto-PGF_1α) 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.     

Prostaglandins and thromboxanes in amniotic fluid during rivanol-induced abortion and labour

Abortion or delivery were induced by extra-amniotic instillation of Rivanol during the second trimester in twelve patients and during the third trimester in two patients with fetal death and one patient with fetal acrania. Serial sampling of amniotic fluid was performed through a transabdominal catheter and the levels of free arachidonic acid (AA), prostaglandin F₂α (PGF₂α), prostaglandin E₂ (PGE₂), 6-keto-prostaglandin F₁α (6-keto-PGF₁α) and thromboxane B₂ (TXB₂) were determined. The levels of AA, PGF₂α, PGE₂, 6-keto-PGF₁α and TXB₂ in amniotic fluid increased significantly during induction with the exception of AA in fetal death which was high and remained constant during induction. Furthermore, PGF₂α, 6-keto-PGF₁α and TXB₂ were all significantly correlated to AA.These observations suggested that free AA is released during Rivanol-induction of abortion and labour giving an increased synthesis of PGF₂α, PGE₂ prostacyclin and thromboxane A₂ in the fetal membranes and the decidua but not in the fetus. This increase might be relevant for the initiation and progress of abortion and labour in these patients.     

Consequences of long-term selenium-deficient diet on the prostacyclin and thromboxane release from rat aorta

It is known that peroxides, which are increased during Se deficiency because of reduced glutathione peroxidase (GSH-Px) activity, can influence the prostacyclin I₂/thromboxane A₂ (PGI₂/TXA₂) ratio. In this study we analyzed the PGI₂ and TXA₂ formation of aortas of long-term Se-deficient rats. Despite low GSH-Px activity in the Se-deficient group, the basal PGI₂ and TXA₂ formation was not different versus control animals (PGI₂: 2295 ± 1134 pg/mg vs 2940 ± 1134 pg/mg; TXA₂: 3.83 ± 1.06 pg/mg vs 5.67 ± 2.99 pg/mg). However, we checked the capacity of the aortas of Se-deficient rats to compensate for a suddenly increased peroxide concentration. After peroxide stimulation, the PGI₂ release was significantly lower in the Se-deficient group compared to the control group (PGI₂: 3507 ± 1829 pg/mg vs 7986 ± 2636 pg/mg). Again, the TXA₂ release did not show any differences. The release ratio of PGI₂/TXA₂ decreased under peroxide stress in Se-deficient animals. Although long-term Se deficiency showed a relatively well-balanced metabolism under resting conditions, sudden stress, accompanied by an excessive radical production, cannot be compensated.     

The high yield of prostacyclin biosynthesis by the iris and its effects on the intraocular muscles

Iris, and to a lesser extent ciliary body , from cat and rabbit produce considerable amounts of prostacyclin (PGI₂) after incubation of the tissue with 1-¹⁴C arachidonic acid. These tissues also generate PGI₂-like material after gentle squeezing. It is likely that major metabolites found previously in iris and aqueous humor actually were 6-keto-PGF_1α. It is concluded that PGH₂ and PGI₂ are synthetized at the same location. PGI₂ induces a contraction of the sphincter and dilator and a relaxation of the ciliary muscle if the tissues had been previously exposed to indomethacin. Thromboxane A₂ (TXA₂) has either no effect or may cause a slight relaxation of the sphincter.