The effects of plasma from IgA nephropathy patients on vascular prostacyclin and platelet cyclic AMP production

The effects of plasma from 10 IgA nephropathy patients and from ten controls were studied on vascular prostacyclin (PGI2) production, the cyclic AMP (cAMP) level and the aggregation of normal platelets. The ability of the plasma to support PGI2-like activity (PSA) was significantly lower in the group of patients (18.0 +/- 13.3%) than in the controls (52.6 +/- 12.9%). The concentration of 6-keto-PGF1 alpha in the supernatant of the vascular tissue was also lower following incubation with patient plasma than with control plasma (p less than 0.001). The reduced PGI2 released by the patient plasma led to a significantly lower platelet cAMP than that following the control plasma (p less than 0.01). There was a significantly positive correlation between the 6-keto-PGF1 alpha and the plasma PSA, and also between both the plasma PSA and 6-keto-PGF1 alpha concentrations and the platelet cAMP level. These findings suggest that a vascular PGI2 defect may cause a reduced cAMP production and an uninhibited aggregation of platelets, which might play a role in the pathogenesis of IgA nephropathy.     

Seminal prostaglandins in men with subnormal sperm motility and therapeutic treatment

The contents of prostaglandins in seminal plasma from a total of 73 men were evaluated. The subjects were grouped as follows: normospermic men, patients with impaired motility, patients with small untreated varicocele and patients with impaired motility and Kallikrein therapy. Sperm density, morphology and motility were examined. High performance reversed phase liquid chromatography (HPLC) in combination with specific radioimmunoassays were used for the determination of PGE2, PGI2 and PGF2 alpha. There was a significant difference (p less than 0.025; F-test) between the PGI2 concentrations in patients with impaired motility (5.6 +/- 1.4 pg/mg protein) and normal men (8.8 +/- 3.7 pg/mg protein). PGE2 and PGF2 alpha were significantly different in patients with varicocele (p less than 0.025, F-test). Wide ranges of prostaglandins occurred in the Kallikrein-group with no significant differences. We conclude that: a) PGI2 is an additional prostaglandin compound in seminal plasma, b) its measurement may not be useful as diagnostic parameter in subfertile men and c) Kallikrein has no influence on the prostaglandin content in seminal plasma and other seminal parameters as motility, motility index and sperm counts.     

Resistin impairs endothelium-dependent dilation to bradykinin, but not acetylcholine, in the coronary circulation

Elevated plasma levels of fat-derived signaling molecules are associated with obesity, vascular endothelial dysfunction, and coronary heart disease; however, little is known about their direct coronary vascular effects. Accordingly, we examined mechanisms by which one adipokine, resistin, affects coronary vascular tone and endothelial function. Studies were conducted in anesthetized dogs and isolated coronary artery rings. Resistin did not change coronary blood flow, mean arterial pressure, or heart rate. Resistin had no effect on acetylcholine-induced relaxation of artery rings; however, resistin did impair bradykinin-induced relaxation. Selective impairment was also observed in vivo, as resistin attenuated vasodilation to bradykinin but not to acetylcholine. Resistin had no effect on dihydroethidium fluorescence, an indicator of superoxide (O(2)(-)) production, and the inhibitory effect of resistin on bradykinin-induced relaxation persisted in the presence of Tempol, a superoxide dismutase mimetic. To determine whether resistin impaired production of and/or responses to nitric oxide (NO) or prostaglandins (e.g., prostacyclin; PGI(2)), we performed experiments with N(omega)-nitro-L-arginine methyl ester (L-NAME) and indomethacin. The effect of resistin to attenuate bradykinin-induced vasodilation persisted in the presence of L-NAME or indomethacin, suggesting resistin may act at a cell signaling point upstream of NO or PGI(2) production. Resistin-induced endothelial dysfunction is not generalized, and it is not consistent with effects mediated by O(2)(-) or interference with NO or PGI(2) signaling. The site of the resistin-induced impairment is unknown but may be at the bradykinin receptor or a closely associated signal transduction machinery proximal to NO synthase or cyclooxygenase.     

The effects of prostacyclin (PGI2) and 6-keto-PGF1 alpha on bovine plasma progesterone and LH concentrations

Injections of 1 mg PGI2 directly into the bovine corpus luteum significantly increased peripheral plasma progesterone concentrations within 5 min. Concentrations were higher in the PGI2-treated heifers than in saline-injected controls between 5 and 150 min and at 3.5, 4, 5, and 7 h post-treatment. Levels tended to remain elevated through 14 h. Saline and 6-keto-PGF1 alpha were without effect on plasma progesterone levels. The luteotrophic effect of PGI2 was not due to alterations in circulating LH concentrations. An in vitro experiment assessed the effects of either PGI2 alone or in combination with LH on progesterone production by dispersed luteal cells. Progesterone accumulation over 2 h for control, 5 ng LH, 1 microgram PGI2, 10 micrograms PGI2, and 10 micrograms PGI2 plus 5 ng LH averaged 99 +/- 42, 353 +/- 70, 152 +/- 35, 252 +/- 45, and 287 +/- 66 ng/ml (n = 4), respectively. Thus PGI2 has luteotrophic effects on the bovine CL both in vivo and in vitro.     

Enhancement of anaphylactic mediator release from guinea-pig perfused lungs by fatty acid hydroperoxides.

Fragments of chopped lung from indomethacin treated guinea-pigs had an anti-aggregating effect when added to human platelet rich plasma (PRP), probably due to the production of prostacyclin (PGI2) since the effect was inhibited by 15-hydroperoxy arachidonic acid (15-HPAA, 10 micrograms ml(-1)). Both 15-HPAA (1-20 micrograms ml(-1) min (-1)) and 13-hydroperoxy linoleic acid (13-HPLA, 20 micrograms ml(-1) min(-1)) caused a marked enhancement of the anaphylactic release of histamine, slow-reacting substance of anaphylaxis (SRS-A) and rabbit aorta contracting substance (RCS) from guinea-pig isolated perfused lungs. This enhancement was not reversed by the concomitant infusion of either PGI2 (5 micrograms ml(-1) min (-1)) or 6-oxo-prostaglandin F1alpha (6-oxo-PGF1alpha, 5 micrograms ml(-1) min(-1)). Anaphylactic release of histamine and SRS-A from guinea-pig perfused lungs was not inhibited by PGI2 (10 ng - 10 microgram ml(-1) min(-1)) but was inhibited by PGE2 (5 and 10 micrograms ml(-1) min (-1)). Antiserum raised to 5,6-dihydro prostacyclin (PGI1) in rabbits, which also binds PGI2, had no effect on the release of anaphylactic mediators. The fatty acid hydroperoxides may enhance mediator release either indirectly by augmenting thromboxane production or by a direct effect on sensitized cells. Further experiments to distinguish between these alternatives are described in the accompanying paper (27).     

Differential effects of prostacyclin and prostaglandin E1 on bronchoconstriction and thrombocytopenia during collagen and arachidonate infusions and anaphylactic shock in the guinea-pig

The antagonism by prostacyclin (PGI2) and prostaglandin E1 (PGE1) of bronchoconstriction induced by serotonin (5HT), collagen, arachidonic acid (AA) and anaphylaxis, as well as of thrombocytopenia was studied in the guinea-pig. Under conditions where PGE1 prevented bronchoconstriction by 5HT, by collagen or by AA better than the accompanying thrombocytopenia, PGI2 was a selective antagonist of bronchoconstriction due to collagen, but failed to interfere with that due to 5HT or to AA. Collagen-induced bronchoconstriction in the guinea-pig is platelet-dependent, being inhibited by immune platelet depletion, whereas that due to AA is platelet-independent. PGI2 blocks bronchoconstriction by collagen, because it prevents the platelet activation, and fails to interfere with bronchoconstriction by AA, even though it reduces the accompanying thrombocytopenia, because the role of platelets is negligible. PGE1 and PGI2 failed to interfere with thrombocytopenia or with bronchoconstriction of anaphylactic shock, and were inactive even when the acute bronchial effect was suppressed by anti-histamine treatment. Anaphylactic thrombocytopenia is beyond the control of agents which stimulate the cyclic AMP system, and involves specific mechanism which are not stimulated in platelet-rich plasma.     

Prostacyclin I2 (PGI2) increases left ventricular ejection fraction (LVEF)

In order to evaluate the effect of PGI2 on left ventricular ejection fraction (LVEF) an intravenous infusion in 10 patients (3 males, 7 females; 36 to 63 years) with an impaired LVEF (34.7 +/- 14.8%) was performed. LVEF was determined by means of 99mTc-pertechnetate radionuclide ventriculography. An increase of LVEF to 36.2 +/- 13.5% during administration of PGI2 at a rate of 1 ng/kg/min for 15 min and to 43.8 +/- 15.8% during a rate of 5 ng/kg/min (p less than 0.01) for an additional 15 min was observed. Analyzing the data in more detail in 6 patients, an improvement in LVEF became obvious during the administration of 1 ng/kg/min (108, 109, 116, 118, 121, and 123% of pre-infusion value, respectively). In 5 out of these 6 patients a dose-increment to 5 ng/kg/min further increased LVEF (139, 179, 187, 148, and 128% of pre-infusion value, respectively). In contrast, in the other 4 patients no response of LVEF to PGI2 at a rate of 1 ng/kg/min could be observed. However, in 2 out of these 4 patients LVEF increased during the administration of 5 ng/kg/min (111 and 117% of pre-infusion value). Individual changes in hemodynamic parameters showed no correlation to the improvement seen in LVEF in response to PGI2. It is concluded that PGI2 may exert beneficial effects on LVEF, and might be used in certain clinical conditions, such as before heart transplantation, to achieve a temporary improvement in LVEF.     

Lack of effect of ischemia and dipyridamole on prostacyclin production in arteriosclerosis obliterans

Six patients with advanced arteriosclerosis obliterans in the lower extremities were subjected to an exercise test on a tread mill with and without dipyridamole treatment. Prostacyclin (PGI2) release was measured by the concentration of its stable metabolite, 6-keto-prostaglandin F1 alpha in plasma. All the patients suffered from ischemic pain during both tests, but no changes were seen in plasma 6-keto-PGF1 alpha. Dipyridamole did not affect the physical performance. Our results suggest that atherosclerotic vessels do not increase PGI2 production in response to ischemia and that a single dose of dipyridamole does not change PGI2 production.     

Production of platelet thromboxane A2 and arterial prostacyclin I2 from hypercholesterolemic rats.

The plasma cholesterol, plasma malonaldehyde (MDA), platelet thromboxane A2 (TXA2) and vascular prostacyclin (PGI2) were measured in male Sprague-Dawley rats fed diets supplemented with cholesterol (1%) and cholic acid (0.5%). For comparisons, measurements were made in rats fed normal diets. The concentration of cholesterol in the plasma of rats had reached a maximum in 1 week of feeding experimental diets. TXA2 production from collagen and thrombin stimulated platelets was significantly decreased in animals fed experimental diets for 1 week. The production of MDA in the plasma of animals fed experimental diets for 8 weeks was significantly lower compared to the animals fed normal diets. There was a small but significant reduction in the formation of PGI2 in rats fed experimental diets for 8 weeks. These data suggest that feeding cholesterol rich diets to rats alters the platelet membrane properties differently from human and rabbit. Furthermore, cholesterol feeding to rats had some damaging effect on the arterial PGI2 synthesis.     

Increased vascular thromboxane generation impairs dilation of skeletal muscle arterioles of obese Zucker rats with reduced oxygen tension

This study determined if altered vascular prostacyclin (PGI(2)) and/or thromboxane A(2) (TxA(2)) production with reduced Po(2) contributes to impaired hypoxic dilation of skeletal muscle resistance arterioles of obese Zucker rats (OZRs) versus lean Zucker rats (LZRs). Mechanical responses were assessed in isolated gracilis muscle arterioles following reductions in Po(2) under control conditions and following pharmacological interventions inhibiting arachidonic acid metabolism and nitric oxide synthase and alleviating elevated vascular oxidant stress. The production of arachidonic acid metabolites was assessed using pooled arteries from OZRs and LZRs in response to reduced Po(2). Hypoxic dilation, endothelium-dependent in both strains, was attenuated in OZRs versus LZRs. Nitric oxide synthase inhibition had no significant impact on hypoxic dilation in either strain. Cyclooxygenase inhibition dramatically reduced hypoxic dilation in LZRs and abolished responses in OZRs. Treatment of arterioles from OZRs with polyethylene glycol-superoxide dismutase improved hypoxic dilation, and this improvement was entirely cyclooxygenase dependent. Vascular PGI(2) production with reduced Po(2) was similar between strains, although TxA(2) production was increased in OZRs, a difference that was attenuated by treatment of vessels from OZRs with polyethylene glycol-superoxide dismutase. Both blockade of PGH(2)/TxA(2) receptors and inhibition of thromboxane synthase increased hypoxic dilation in OZR arterioles. These results suggest that a contributing mechanism underlying impaired hypoxic dilation of skeletal muscle arterioles of OZRs may be an increased vascular production of TxA(2), which competes against the vasodilator influences of PGI(2). These results also suggest that the elevated vascular oxidant stress inherent in metabolic syndrome may contribute to the increased vascular TxA(2) production and may blunt vascular sensitivity to PGI(2).     

Eicosanoid and cytokine levels in plasma of patients during mesenteric infarction

Multible organ failure (MOF) induced by mesenteric infarction is associated with a high mortality rate. This study reports eicosanoid and cytokine levels in the blood of three atherosclerotic patients who ultimately died from MOF induced by mesenteric infarction. High plasma levels of 6- keto-prostaglandin (PG) F(1alpha) (the stable metabolite of PGI(2)), interleukin (IL)-6 and IL-8 are observed whereas plasma tumour necrosis factor alpha (TNFalpha), TxB(2) (the stable metabolite of TxA(2)), PGE(2), leukotrienes (LT)B(4) and LTC(4), and whole blood platelet-activating factor levels are not different from values obtained in similarly severe atherosclerotic patients. This short report questioned the clinical involvement of TNFalpha during such a pathology where a persistent translocation of endotoxin has been observed through the gut endothelial barrier. Activation of phospholipase A(2) is suggested by the increase in the stable metabolite of PGI(2) and might be by itself or through lipidic metabolites, a major systemic stimulus of IL-6 and IL-8 production.     

Influence of verapamil on central and peripheral effects of prostacyclin on circulatory system in rats

The influence of verapamil on cardiovascular effects of prostacyclin (PGI2) in rats was examined. PGI2 administered into the lateral brain ventricle (i.c.v.) or intravenously (i.v.) in a dose of 2.7 x 10(-8)mol evoked hypotension and tachycardia. Pretreatment with verapamil in a dose of 2.0 x 10(-5)mol/kg given intraperitoneally (i.p.) diminished hypotensive effect of PGI2 i.c.v. as well as inhibiting the influence of PGI2 i.c.v. and i.v. upon the heart rate. Bolus injection of PGI2 in a dose of 2.7 x 10(-10), 2.7 x 10(-9) or 2.7 x 10(-8)mol evoked biphasic inotropic and chronotropic effects on isolated rat heart. Short-term increase of the contractile force together with bradycardia and afterwards long-lasting decrease of contractility with sustained, slight tachycardia were observed. Verapamil in a concentration of 1.0 x 10(-6)M blocked biphasic inotropic effect and bradycardia after PGI2 administration. Because some central and peripheral cardiovascular effects of PGI2 were inhibited by verapamil, it is concluded that PGI2 may participate in transmembrane calcium ions movements.     

High density lipoprotein-induced cardiac prostacyclin synthesis in vitro: relationship to cardiac arachidonate mobilization

The objectives of this study were to characterize the effects of plasma lipoproteins on prostacyclin (PGI2) production by the Langendorff-perfused rabbit heart, and to determine the mechanism of lipoprotein-induced cardiac PGI2 production. PGI2 production by perfused rabbit hearts was stimulated by injections of rabbit very low density lipoproteins (VLDL), low density lipoproteins (LDL), and high density lipoproteins (HDL). HDL was much more effective than equivalent doses of VLDL or LDL. Infusion of HDL at a physiological concentration stimulated cardiac PGI2 output by 417%, but infusion of VLDL or LDL was ineffective. Cardiac PGI2 production increased from 47% to 340% with increasing doses of HDL. The release of cardiac PGI2 in response to injections or infusions of HDL occurred rapidly; maximal release of PGI2 was reached within 2 min after exposure to HDL. Injections of HDL stimulated the production of [3H]arachidonic acid, [3H]prostaglandin E2, [3H]prostaglandin F2 alpha, and [3H]6-keto-prostaglandin F1 alpha from hearts after prelabeling of cardiac lipids with [3H]arachidonic acid. These results indicate that plasma lipoproteins, specifically HDL, stimulate PGI2 production by the isolated rabbit heart. The mechanism by which HDL increases cardiac PGI2 production may involve the mobilization of cardiac arachidonic acid for PGI2 synthesis.     

Modulation of vascular thrombosis by products of arachidonic acid metabolism

It has been postulated that metabolites of the arachidonic acid pathway exert an important influence on hemostasis and thrombosis. This notion is based on in vitro experiments. We have utilized two experimental models to elucidate the physiologic roles of thromboxane A2 (TxA2) and prostacyclin (PGI2) in the modulation of thrombus formation. The role of TxA2 in promoting thrombus formation was evaluated in a rabbit model where the aorta was deendothelialized by a balloon catheter technique and indium-111-labeled platelets were used as a marker for quantifying platelet deposition. Both 1-benzylimidazole, a thromboxane synthase inhibitor, and 13-azaprostanoic acid, an antagonist of thromboxane/endoperoxide receptors significantly reduced the platelet deposition onto the damaged vessel wall. The data indicate the TxA2 plays an important role in thrombosis and hemostasis. The influence of PGI2 insufficiency due to accelerated PGI2 degradation on microvascular thrombosis was evaluated in a unique clinical disease, i.e. thrombotic thrombocytopenic purpura (TTP). Accelerated PGI2 degradation was observed in several patients with chronic TTP. The degradation abnormalities were corrected by plasma infusion in vivo or serum supplement in vitro. To test the hypothesis that PGI2 must be bound to serum macromolecules to prevent rapid hydrolysis, serum binding capacity for PGI2 was measured by Sephadex G-25 gel filtration. The binding capacity was significantly reduced in the patients and was corrected by serum supplement. Abnormalities of PGI2 binding were also noted in a group of patients with ischemic stroke. Our findings suggest that there exist in the serum certain constituents which bind and stabilize PGI2.(ABSTRACT TRUNCATED AT 250 WORDS)     

Prostaglandin synthesis by fetal rat bone in vitro: evidence for a role of prostacyclin.

Prostaglandin synthesis by fetal rat bones was examined by thin-layer chromatography of culture media after preincubation with labeled arachidonic acid. Cultures in rabbit complement (non-heat inactivated serum) were compared with cultures in heat-inactivated serum or cultures treated with indomethacin. The major complement-dependent products were PGE2, PGF2 alpha and 6-keto-PGF1 alpha, the metabolite of prostacyclin (PGI2). Since PGI2 had not been previously identified in bone its ability to stimulate bone resorption was tested. Repeated addition of PGI2 stimulated release of previously incorporated 45Ca from fetal rat long bones in both short-term and long-term cultures at concentrations of 10(-5) to 10(-9)M. Because of the short half life of PGI2 in solution at neutral pH, we tested a sulfur analog, thiaprostacyclin (S-PGI2) which was found to be a stimulator of bone resorption at concentrations of 10(-5) to 10(-6)M. These studies suggest that endogenous PGI2 production may play a role in bone metabolism. Since vessels produce PGI2 it is possible that PGI2 release may be responsible for the frequent association between vascular invasion and resorption of bone or calcified cartilage in physiologic remodeling and pathologic osteolysis.     

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-PGF1 alpha 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-PGF1 alpha 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-PGF1 alpha. 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-PGF1 alpha 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.     

Low-dose PGI2 prevents monocrotaline-induced thromboxane production and lung injury

In animals, monocrotaline induces an acute lung injury secondary to capillary endothelial damage. To date, no reports have appeared dealing with the role of prostaglandins in monocrotaline-induced injury. Our studies, in dogs, revealed that monocrotaline (30 mg/kg iv) caused an acute and persistent thrombocytopenia, lung platelet deposition, pulmonary hypertension, and increased extravascular lung water (EVLW). The pulmonary hypertensive response was biphasic. Thromboxane B2 levels were similarly biphasic, peaking at 5 min and 2 h. The levels of 6-keto-PGF1 alpha peaked at 30 min and returned to base line at 3 h. Pulmonary vascular resistance paralleled thromboxane levels. Infusion of prostacyclin (PGI2) at 50 ng X kg-1 X min-1 effectively prevented the thrombocytopenia, lung platelet deposition, pulmonary hypertension, and increased EVLW; and it decreased excess thromboxane production by 79%. These results suggest that platelet activation and lung sequestration play a role in acute lung injury due to monocrotaline, and that the resultant thromboxane production may contribute to the pulmonary hypertension. PGI2 ameliorates monocrotaline-induced injury, perhaps by preventing platelet activation.     

Effect of human plasma lipoproteins on prostacyclin production by cultured endothelial cells

Prostacyclin (PGI2) production by bovine aortic or human umbilical vein endothelial cells increased when either human high density lipoproteins3 (HDL3) or low density lipoproteins (LDL) were added to a serum-free culture medium. At low concentrations and short incubation times, HDL3 produced more PGI2 than LDL, but LDL was just as effective as HDL3 in 18-hr incubations with high concentrations of lipoproteins. Neither lipoprotein was toxic to the cultures as assessed by [3H]leucine incorporation into cell protein. The stimulatory effect of HDL3 and LDL on PGI2 production decreased as growing cultures became confluent. Incubation with lipoproteins neither enhanced arachidonic acid release nor increased PGI2 formation when the cells were stimulated subsequently with ionophore A23187, indicating that the lipoproteins do not affect the intracellular processes involved in PGI2 production. The addition of albumin reduced the amount of PGI2 formation elicited by HDL3 or LDL. As compared with albumin-bound arachidonic acid, from 6- to 13-fold less PGI2 was produced during incubation with the lipoproteins. Furthermore, the amount of PGI2 formation elicited by the lipoproteins in 18 hr was 4-fold less than that produced during incubation with a fatty acid mixture containing only 5% arachidonic acid, and 3-fold less than when the cells were stimulated with the ionophore A23187 for 20 min. Taken together, our results indicate that human HDL and LDL contribute to endothelial PGI2 production only in a modest way and suggest that this process is not specific for either of these two plasma lipoproteins. In view of the greater participation of albumin-bound arachidonic acid in PGI2 production, plasma lipoproteins may not play as important a role in endothelial prostaglandin formation as has been suggested.     

Epoprostenol in patients with Raynaud's disease

Prostaglandin metabolism and the clinical effect of epoprostenol (prostacyclin, PGI2) infusions were studied in thirteen patients with Raynaud's disease. Epoprostenol was infused at 5 ng/kg/min for six hours daily for two consecutive five day periods, separated by a two day interval. No beneficial effects either during or after infusion could be detected in terms of frequency of severity of attacks or on skin temperature measurement. Raynaud's patients had significantly lower serum thromboxane B2 levels than normal controls though plasma levels of thromboxane B2, 6-oxo-PGF1 and the bicyclic metabolite of PGE2 did not differ between the two groups. Platelets from Raynaud's patients had a significantly lower conversion rate of arachidonic acid into thromboxane B2 and HHT and a significantly higher rate of HETE production than platelets from controls.