PubMed Health⌕ Search

Biomedical subjects

J C Frölich

Publications and source records attributed to J C Frölich.

At least 91 records · Page 5Linked to original sources
PubMed1996

L-arginine induces nitric oxide-dependent vasodilation in patients with critical limb ischemia. A randomized, controlled study.

BACKGROUND: L-Arginine is the precursor of endogenous nitric oxide (NO), which is a potent vasodilator acting via the intracellular second-messenger cGMP. In healthy humans, L-arginine induces peripheral vasodilation and inhibits platelet aggregation due to an increased NO production. Prostaglandin E1 (PGE1) induces peripheral vasodilation via stimulating prostacyclin receptors. METHODS AND RESULTS: We investigated the effects of one intravenous infusion of L-arginine (30 g, 60 minutes) or PGE1 (40 microgram, 60 minutes) versus those of placebo (150 mL 0.9% saline, 60 minutes) on blood pressure, peripheral hemodynamics, and urinary NO3- and cGMP excretion rates in patients with critical limb ischemia (peripheral arterial occlusive disease stages Fontaine III or IV). Blood flow in the femoral artery was significantly increased by L-arginine (+42.3 +/- 7.9%, P<.05) and by PGE1 (+31.0 +/- 10.2%, P<.05) but not by placebo (+4.3 +/- 13.0%, P=NS). Urinary NO3- excretion increased by 131.8 +/- 39.5% after L-arginine (P<.05) but only by 32.3 +/- 17.2% after PGE1 (P=NS). Urinary cGMP excretion increased by 198.7 +/- 84.9% after L-arginine (P<.05) and by 94.2 +/- 58.8% after PGE1 (P=NS). Both urinary index metabolites were unchanged by placebo. CONCLUSIONS: We conclude that intravenous L-arginine induces NO-dependent peripheral vasodilation in patients with critical limb ischemia. These effects are paralleled by increased urinary NO3- and cGMP excretion, indicating an enhanced systemic NO production. Increased urinary NO3- excretion may be a sum effect of NO synthase substrate provision (L-arginine) and increased shear stress (PGE1 and L-arginine).

Aged↗
PubMed1996

Effects of ketoprofen and ibuprofen on platelet aggregation and prostanoid formation in man.

OBJECTIVE: In the present randomized, fourway crossover study we determined the effects of two oral doses each of ketoprofen and ibuprofen on platelet aggregation and prostanoid formation in man. METHODS: Twelve healthy female volunteers received for 2 consecutive days, followed by a 5-day drug-free interval, one of the following: ketoprofen 3 x 25 mg per day, or ketoprofen 3 x 50 mg per day, or ibuprofen 3 x 200 mg per day, or ibuprofen 3 x 400 mg per day. The response criteria, determined before and on the 2nd day of each treatment period, were: maximal platelet aggregation in response to 1.0 mmol.l-1 arachidonic acid measured by the method of Born and Cross, thromboxane B2 (TXB2) concentration in platelet-rich plasma after aggregation measured by radioimmunoassay, and PGE-M, the index metabolite of total body prostaglandin E2 (PGE2) production, assessed by gas chromatography/tandem mass spectrometry using 18O2-PGE-M as internal standard. RESULTS: Platelet aggregation was significantly reduced by ketoprofen 3 x 25 mg per day (-57%) and ketoprofen 3 x 50 mg per day (-85%) as compared to control, whereas ibuprofen 3 x 200 mg per day (-3%) and ibuprofen 3 x 400 mg per day (-22%) had no significant effects. TXB2 synthesis was significantly decreased by ketoprofen 3 x 25 mg per day (-72%), ketoprofen 3 x 50 mg per day (-97%) and ibuprofen 3 x 400 mg per day (-48%) as compared to control; ibuprofen 3 x 200 mg per day did not reduce TXB2 formation significantly (-23%). All four treatments reduced 24-h urinary excretion of PGE-M significantly in the range of -39% (ketoprofen 3 x 25 mg per day) to -53% (ibuprofen 3 x 400 mg per day) without significant differences between treatments. CONCLUSION: Our data show that both ketoprofen dosages were more effective in inhibition of platelet aggregation and platelet thromboxane synthesis than ibuprofen in low or high dosage. Total body synthesis of the E-prostaglandins was inhibited by all drug schedules without significant differences between treatments.

Adult↗
PubMed1996

A new bioassay to study contractile and relaxant effects of PGE2 on perfused guinea pig trachea.

The aim of this study was to investigate the effects of PGE2 under different experimental conditions. By a newly developed imaging bioassay system, changes of the diameter of isolated perfused guinea-pig tracheal tubes were continuously measured. The results were compared with those of a conventional ring bioassay system. The effect of PGE2 was examined in epithelium-intact and-denuded tubes. The potency of PGE2 applied to the inner surface of tube preparations was significantly enhanced by about six-fold in epithelium-denuded compared with epithelium-intact tubes. In rings there was no difference. The results suggest a potential role of epithelium in assessment of airway reactivity in vivo. The study demonstrates, that the effects of PGE2 depend critically on the experimental approach. PGE2 (0.01 nmol 1(-1)-1 mumol 1(-1)) contracted tracheal tubes, but resulted in relaxation of ring preparations under basal tone. The spontaneous tone of guinea pig trachea can be reduced with the cyclooxygenase inhibitor diclofenac. Pretreatment of the rings with diclofenac reversed the relaxation into contraction. Preincubation of tube preparations with diclofenac had no effect on basal tone, indicating that there was no inherent spontaneous prostanoid-dependent tone or the mediators may be washed out at a relatively fast rate and, therefore, tone may not be apparent.

Analysis of Variance↗
PubMed1996

Recombinant human erythropoietin enhances vasoconstrictor tone via endothelin-1 and constrictor prostanoids.

Hypertension is the main side effect developing in patients suffering from renal anemia who are treated with recombinant human erythropoietin (rHuEPO). We investigated the effect of rHuEPO on the vascular tone of isolated rabbit aorta and carotid artery under isometric conditions. The production of prostacyclin and the vasoconstrictor prostanoids PGF2 alpha and TXB2 was investigated in arterial rings incubated with rHuEPO. Endothelial cells from human umbilical veins (HUVECs) were isolated and cultured in flasks (37 degrees C, 5% CO2). After incubation with rHuEPO, the formations of prostacyclin (as its stable metabolite 6-keto-PGF1 alpha), PGF2 alpha, PGE2, thromboxane (TX) B2 and of ET-1 were measured by radioimmunoassays. rHuEPO had no direct vasoconstrictor effect, but it enhanced noradrenalin-induced contractions. This effect was more prominent in rings with intact endothelium than in rings from which the endothelium had been mechanically removed, indicating that endothelial vasoactive factors might be involved. Relaxations to acetylcholine (ACh, 1 microM) were unaltered in the presence or absence of rHuEPO, suggesting that the endothelial NO-cGMP pathway was not impaired by rHuEPO. Incubation with rHuEPO (20 to 200 U/ml) increased the release of the vasoconstrictor mediators ET-1, PGF2 alpha and TXB2, and decreased prostacyclin formation in isolated rabbit arterial rings and in HUVECs, respectively. The cyclooxygenase inhibitor indomethacin abolished the rHuEPO-induced increase in vasoconstrictor prostanoid production. ET-1 formation by HUVECs was also increased by rHuEPO in a dose-dependent manner (maximal effect +90% by rHuEPO 200 U/ml, P < 0.05). Indomethacin and the selective ETA receptor antagonist BQ123 each partly inhibited the enhancement of vascular responsiveness to noradrenalin induced by rHuEPO in rabbit carotid artery, but simultaneous administration of rHuEPO with both antagonists completely abolished the force increment. In conclusion, these studies show that a dose-dependent shift in the balance of constrictor and relaxing prostanoids as well as an increased synthesis of ET-1 induced by rHuEPO lead to the enhanced vascular responsiveness to noradrenalin in isolated rabbit arteries. The increased vascular responsiveness to noradrenalin, which is in line with clinical observations, may contribute to the hypertensive side effect associated with rHuEPO therapy in patients with chronic renal failure.

Acetylcholine↗
PubMed1996

Effect of captopril on prostacyclin and nitric oxide formation in healthy human subjects: interaction with low dose acetylsalicylic acid.

1. Angiotensin converting enzyme inhibitors have been suggested to act in part by potentiating the stimulatory effect of bradykinin on endothelial prostacyclin and/or nitric oxide (NO) formation. This may give rise to interaction with cyclo-oxygenase inhibiting drugs like acetylsalicylic acid, which is most often used in low doses in patients with cardiovascular diseases. 2. We investigated the effects of captopril (2 x 25 mg day-1), or ASA (1 x 100 mg day-1), or the combination of both drugs for 7 days, on blood pressure, prostanoid and NO formation rates in a double-blind, double dummy, randomized crossover study in 13 healthy female subjects. The urinary metabolites of thromboxane A2 (2,3-dinor-TXB2) and prostacyclin (2,3-dinor-6-keto-PGF1 alpha), and PGE2 were measured by gas chromatography/tandem mass spectrometry in urine on days 1, 6 and 7 of each medication. NO formation was assessed using urinary NO3- and cyclic GMP as indicators. 3. Urinary 2,3-dinor-6-keto-PGF1 alpha excretion was not significantly changed by either captopril, ASA, or their combination. Urinary 2,3-dinor-TXB2 excretion was inhibited by > 80% by ASA alone or in combination with captopril (each P < 0.05), but was not affected by captopril alone. Urinary PGE2 excretion was not significantly changed by either of the treatments. Urinary NO3- and cyclic GMP excretion rates were not significantly changed by captopril, ASA, or their combination. 4. Blood pressure was slightly reduced by captopril. ASA had no effect on blood pressure when given alone, nor did it modulate the effect of captopril on blood pressure during co-administration. Angiotensin II/angiotensin I ratio (index of ACE activity) was significantly decreased by captopril alone or in combination with ASA, but was unaffected by ASA alone. 5. Captopril does not stimulate prostacyclin formation in healthy human subjects in a dose sufficient to substantially inhibit ACE activity. Co-administration of ASA significantly inhibits 2,3-dinor-TXB2 excretion, but does not interfere with the blood pressure lowering effect of captopril in healthy human subjects.

Adult↗
PubMed1996

Platelet aggregation, sensitivity to prostaglandin E1 and thromboxane A2 release in recombinant hirudin- and heparin-anticoagulated blood.

Hirudin is the most potent known natural inhibitor of thrombin and is presently gaining popularity as an anticoagulant since recombinant forms have become available. The aim of the present study was to compare platelet aggregation, sensitivity to prostaglandin E1 and thromboxane A2 release in r-hirudinized and heparinized blood. Platelet aggregation was measured turbidimetrically using a dual channel aggregometer (Labor, Germany) in blood samples of healthy volunteers anticoagulated with r-hirudin W015 (Behring) and heparin (20 micrograms/ml blood each). Aggregation was induced by arachidonic acid (0.5, 1.0 and 2.0 mM) and adenosine diphosphate (1.0 microM). Prostaglandin E1 in concentrations 10, 20, 40 and 80 ng/ml was used. Plasma thromboxane B2 content was measured by gas chromatography/mass spectrometry. This study showed a significantly lower arachidonic acid induced platelet aggregation in r-hirudinized plasma. Three minutes after the aggregation induction by 0.5 mM arachidonic acid the plasma thromboxane B2 concentration was 23.0 ng/ml in blood anticoagulated with r-hirudin and 108.4 ng/ml in heparin-anticoagulated blood. The extent of the aggregation induced by adenosine diphosphate was nearly the same in hirudinized and heparinized plasma. Platelet sensitivity to prostaglandin E1 was significantly higher in r-hirudinized blood. Thus, platelet aggregation induced by arachidonic acid is significantly lower and sensitivity to prostaglandin E1 higher in r-hirudin-anticoagulated blood in comparison with heparin-anticoagulated blood.

Adenosine Diphosphate↗
PubMed1996

Helicobacter pylori produces histamine and spermidine.

The mechanism by which Helicobacter pylori associates with the development of upper gastrointestinal diseases is still not well understood. Toxic metabolites of H. pylori are discussed as possible factors. We were interested to investigate, whether biogenic amines might be involved. Ten monocultures of H. pylori from the antrum of patients with H. pylori associated diseases were analyzed for the content of the biogenic amine histamine. The bacteria were isolated on Columbia blood agar with Skirrow's supplement in a microaerophilic environment. After three passages onto fresh agar plates the bacteria were harvested in their sonicated suspensions analyzed by reversed-phase high-performance liquid chromatography (HPLC) and gas chromatography-mass spectrometry (GC-MS). From the HPLC analysis, histamine was found in six cultures. Analysis with GC-MS, however, revealed the presence of histamine in all the cultures (0.1-1.63 nmol histamine/10(8) bacteria). Additionally to histamine, all cultures were found to contain spermidine in concentrations of 0.010-7.912 nmol/10(8) bacteria. It is discussed that histamine produced by H. pylori may be involved in the pathogenesis of H. pylori associated gastrointestinal diseases.

Adult↗
PubMed1996

Urinary nitrate excretion is increased in cardiac transplanted patients with acute graft rejection.

Acute allograft rejection in patients after cardiac transplantation is associated with intense infiltration of inflammatory cells. It has been shown in animal studies that this inflammatory process is accompanied by an induction of nitric oxide syndrome (NOS) enzyme within the grafted organ. We sought to test the hypothesis that acute rejection in cardiac transplanted patients is associated with an increased production of nitric oxide. The radical nitric oxide is unstable in blood and oxidized to nitrite and nitrate; nitrate is secreted by the kidneys. Therefore, nitric oxide production was indirectly assessed by measuring urinary nitrate excretion. During a period of 1 yr, 86 consecutive patients after cardiac transplantation underwent one or more right heart biopsies (total 194) in order to assess for acute graft rejection. At the time of biopsies, urine was collected under sterile conditions. Urinary nitrate excretion was expressed as the ratio of nitrate to creatinine concentration in the urine (mumol/ mmol). Urinary nitrate excretion was 99.7 +/- 9.2 (mean +/- SEM) for patients without evidence of rejection, and tended to increase for patients with moderate/severe rejection (128 +/- 15.1). In a subgroup of patients who underwent several biopsies and showed different degrees of rejection (7 patients, 48 biopsies), urinary nitrate excretion significantly increased by about 99% during episodes of acute rejection. It is concluded that urinary nitrate excretion appears to be elevated in a subgroup of cardiac transplanted patients during episodes of acute rejection. Results are consistent with the hypothesis that acute graft rejection stimulates the production/release of nitric oxide. Because of a large inter- and intraindividual variation in urinary nitrate excretion, this parameter appears not to be suitable for diagnosis of acute rejection in cardiac transplanted patients.

Acute Disease↗
PubMed1996

Differential systemic and pulmonary hemodynamic effects of L-arginine in patients with coronary artery disease or primary pulmonary hypertension.

The endothelial EDRF/NO-mediated relaxing mechanism is impaired in atherosclerotic and in hypertensive arteries. Recently, it was suggested that primary pulmonary hypertension might be another disease in which the endothelial EDRF/NO pathway is disturbed. We tested the hypothesis that intravenous administration of L-arginine (L-ARG), the physiological precursor of EDRF/NO, stimulates the production of NO, subsequently increasing plasma cGMP levels and reducing systemic and/or pulmonary blood pressure, in patients with coronary artery disease (CAD, n = 16) or with primary pulmonary hypertension (PPH, n = 5). L-ARG (30 g, 150 ml, 15 min) or placebo (150 ml NaCl) was infused in CAD patients, and L-ARG was infused in PPH patients during cardiac catheterization. Mean aortic (Pao) and pulmonary (PAPmean) arterial pressures were continuously monitored. Cardiac output (CO, by thermodilution), total peripheral resistance (TPR), and pulmonary vascular resistance (PVR) were measured before and during the infusions. In CAD patients Pao decreased from 87.2 +/- 4.9 to 81.8 +/- 5.1 mmHg during L-ARG (p < 0.05), whereas PAPmean and PVR were unchanged. TPR decreased from 1008.9 +/- 87.9 to 845.0 +/- 81.7 dyne x sec x cm-5 during L-ARG administration (p < 0.01). CO significantly increased during L-ARG (from 7.3 +/- 2.8 to 8.1 +/- 0.9 l/min, p < 0.05). Placebo did not significantly influence any of the hemodynamic parameters. Plasma cGMP (determined by RIA) slightly increased by 12.2 +/- 9.6% during L-ARG, but slightly decreased during placebo (-12.3 +/- 9.2%) (p < 0.05 for L-ARG vs. placebo). In PPH patients, L-ARG induced no significant change in Pao, TPR, and CO, PAPmean was 59.4 +/- 8.5 mmHg at the beginning of the study and was not significantly reduced by L-ARG nor was PVR (basal: 1042.4 +/- 211.4 dyne x sec x cm-5) changed by L-ARG. Plasma cGMP was not significantly affected by L-ARG in these patients. We conclude that L-ARG stimulates NO production and induces vasorelaxation in CAD patients but not in patients with primary pulmonary hypertension.

Adult↗
PubMed1996

[Pathogenetic aspects of the L-arginine-NO metabolic pathway in arteriosclerosis and possible therapeutic aspects].

L-arginine is the physiological precursor of nitric oxide (NO) which is formed in endothelial cells by the activity of the constitutive NO synthase isoenzyme. NO is tonically released from the endothelium, thus maintaining an active vasodilator tone and inhibiting platelet aggregation, leukocyte adhesion, and vascular smooth muscle cell proliferation. In experimental hypercholesterolemia and atherosclerosis as well as in hypercholesterolemic patients, NO-mediated responses have been shown to be impaired. Whether decreased formation and/or enhanced oxidative inactivation are involved in this process, is still unclear. Chronic dietary administration of L-arginine has been shown to exert anti-atherosclerotic effects in hypercholesterolemic rabbits. Intravenous infusion of L-arginine induces NO-dependent peripheral vasodilatation and inhibits platelet aggregation in healthy humans as well as in patients with severe limb ischemia and generalized atherosclerosis. Whether L-arginine may induce therapeutic effects in peripheral vascular disease, still remains unclear.

Animals↗
PubMed1995

Chemical synthesis of dioxygen-18 labelled omega-/beta-oxidized cysteinyl leukotrienes: analysis by gas chromatography-mass spectrometry and gas chromatography-tandem mass spectrometry.

Cysteinyl leukotrienes (LT) C4, LTD4 and LTE4 are potent mediators of anaphylaxis and inflammation. LTE4 is extensively metabolized in man mainly by omega-oxidation followed by subsequent beta-oxidation to more polar and biologically inactive metabolites. This paper describes a method for the synthesis of [1,20-18O2]-carboxy-LTE4, [1,18-18O2]-carboxy-dinor-LTE4, and [1,16-18O2]-carboxy-14,15-dihydro-tetranor-LTE4 starting from the unlabelled dimethyl esters of 20-carboxy-LTA4, 18-carboxy-dinor-LTA4 and 16-carboxy-14,15-dihydro-tetranor-LTA4, respectively, by separate chemical conjugation with cysteine hydrochloride in H2-18O-methanol followed by alkaline hydrolysis with Li18OH. The isotopic purity of the isolated reaction products was 94% at 18O for all three preparations while only 0.3% remained unlabelled as confirmed by negative-ion chemical-ionization gas chromatography-mass spectrometry (GC-NICI-MS) after their catalytical reduction/desulphurization and derivatization. The 18O2-labelled compounds are demonstrated to be suitable internal standards for quantification by GC-NICI-MS and GC-NICI-tandem MS. We found by GC-NICI-tandem MS that the excretion rate of 20-carboxy-LTE4 is comparable to that of LTE4 (both in nmol/mol creatinine, mean +/- S.E.) in healthy children (26.7 +/- 4.7 vs. 32.0 +/- 6.0, n = 9) and adults (13.9 +/- 1.1 vs. 27.2 +/- 5.4, n = 3).

Adult↗
PubMed1995

Supplementation of hypercholesterolaemic rabbits with L-arginine reduces the vascular release of superoxide anions and restores NO production.

L-arginine, the precursor of endogenous nitric oxide (NO), has been shown to enhance endothelial function and to reduce intimal plaque area in cholesterol (Chol)-fed rabbits. We have studied endogenous NO production in such animals in vitro (endothelium-dependent relaxations) and in vivo (assessed by urinary NO3- excretion) before and during chronic oral administration of L-arginine and inhibitor of NO synthesis, L-NAME. Vascular superoxide anion (O2-) production of aortic rings was measured under basal conditions and following exposure to phorbol-myristate-acetate (PMA). Cholesterol feeding reduced endothelium-dependent relaxations and decreased urinary NO3- excretion. These effects were potentiated by administration of L-NAME. L-arginine partly restored endothelium-dependent relaxations and increased NO3- excretion. PMA-stimulated O2- production was increased in aortic rings from rabbits given cholesterol ( +159 +/- 28%; mean +/- S.E.M.) or cholesterol + L-NAME ( +149 +/- 37%) as compared with controls ( -22 +/- 7%). In rabbits given cholesterol + L-arginine, O2- production was decreased to control levels ( +14 +/- 17%; P < 0.05). We conclude that the systemic synthesis of NO is impaired in cholesterol-fed rabbits, as indicated by the decreased urinary excretion of NO3-. Enhanced O2- production may further contribute to the decreased biological activity of NO in hypercholesterolaemia. L-arginine restores endothelial function in hypercholesterolaemia by enhancing NO production and by protecting NO from early breakdown by O2-.

Acetylcholine↗
PubMed1995

Use of ibuprofen and methylprednisolone for the prevention of pain and swelling after removal of impacted third molars.

PURPOSE: To test a combination treatment of ibuprofen and methylprednisolone for pain and swelling. METHODS: The efficacy of 32 mg methylprednisolone on pain and swelling when given 12 hours before and after surgery in combination with 400 mg ibuprofen three times a day given immediately on the day of the operation and on the two subsequent days following removal of impacted third molars was investigated in a placebo-controlled, intraindividual double-blind study. RESULTS: After use of ibuprofen/methylprednisolone, ultrasonic examination showed a reduction in swelling of 56% (P < .001) compared with the placebo group; measurement with a tape measure showed a 58% (P < .001) reduction in swelling. The visual analog scale showed a reduction of 67.7% in postoperative pain in comparison with placebo. CONCLUSION: The combination of ibuprofen and methylprednisolone has good analgesic and antiinflammatory action.

Adolescent↗
PubMed1995

Elevated serum nitrate concentrations in active spondyloarthropathies.

We determined the concentrations of nitrate, reflecting endogenous nitric oxide (NO) production, by gas chromatography in the sera of patients with spondyloarthropathy. In those patients with active disease, as indicated by elevated C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) serum nitrate levels (n = 7; mean 73.2 +/- s.d. 21.7 mumol/l) were significantly (P < 0.001) increased in comparison to patients with inactive spondyloarthropathy (n = 7; 31.7 +/- 9.5 mumol/l) and healthy volunteers (n = 10; 33.4 +/- 15.9 mumol/l). The nitrate serum levels correlated closely with CRP and ESR (r = 0.8, P < 0.001, each). There were no major differences in dietary nitrate intake between the study groups. The increased concentrations of serum nitrate in patients with active spondyloarthropathy indicate that NO production is enhanced in these patients.

Adult↗
PubMed1995

Urinary nitrate excretion is increased in patients with rheumatoid arthritis and reduced by prednisolone.

OBJECTIVES: To determine daily production of nitric oxide (NO) measured as urinary nitrate excretion, and the effect of prednisolone in patients with rheumatoid arthritis (RA). METHODS: Twenty four hour urinary nitrate was measured by gas chromatography in 10 patients with RA, before and two to four weeks after commencement of prednisolone 0.5 mg/kg body weight, and in 18 healthy controls. RESULTS: Before the start of prednisolone treatment the urinary nitrate excretion in patients with RA was 2.7-fold greater (p < 0.001) than that in healthy volunteers. After prednisolone it decreased significantly, by 28%, at which time inflammatory activity (as indicated by C reactive protein, erythrocyte sedimentation rate, joint count, and early morning stiffness) was also reduced considerably. Despite this decrease, the urinary nitrate excretion in patients with RA remained twice that in the control group (p < 0.05). CONCLUSIONS: Our data suggest that the endogenous production of NO is enhanced in patients with RA. Furthermore, the results indicate that, in parallel with suppression of inflammation, this increased NO synthesis could be reduced by prednisolone treatment.

Adult↗
PubMed1995

Increased prostacyclin production during exercise in untrained and trained men: effect of low-dose aspirin.

The influence of a submaximal exercise on urinary 2,3-dinor-6-ketoprostaglandin F1 alpha (2,3-dinor-6-keto-PGF1 alpha), 2,3-dinor-thromboxane B2 (2,3-dinor-TxB2), and prostaglandin E2 excretion and on platelet aggregation was compared in untrained and trained subjects before and after low-dose aspirin administration (50 mg/day, 7 days). 2,3-Dinor-TxB2 excretion was significantly higher in the athletes at rest (P < 0.05). Submaximal exercise selectively increased 2,3-dinor-6-keto-PGF1 alpha excretion without affecting 2,3-dinor-TxB2 or prostaglandin E2 excretion rates or platelet aggregation. Low-dose aspirin inhibited platelet aggregation and 2,3-dinor-TxB2 excretion but reduced 2,3-dinor-6-keto-PGF1 alpha by only 24% in the untrained and by 51% in the trained subjects (P < 0.05). After low-dose aspirin administration, the selective stimulatory effect of submaximal exercise on urinary 2,3-dinor-6-keto-PGF1 alpha excretion was even more pronounced than before. The ratio of 2,3-dinor-6-keto-PGF1 alpha to 2,3-dinor-TxB2 was increased by exercise; this effect was significantly enhanced by low-dose aspirin (P < 0.05). Our results suggest that the stimulatory effect of submaximal exercise on prostacyclin production is mostly due to an activation of prostacyclin synthesis from endogenous precursors rather than the result of an enhanced endoperoxide shift from activated platelets to the endothelium. This effect is potentiated by low-dose aspirin pretreatment, indicating that 50 mg/day of aspirin do not impair exercise-induced endothelial prostacyclin production.

6-Ketoprostaglandin F1 alpha↗