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Biomedical subjects

G A Fitzgerald

Publications and source records attributed to G A Fitzgerald.

At least 37 records · Page 2Linked to original sources
PubMed1994

Effects of dietary fat content, saturated fatty acids, and fish oil on eicosanoid production and hemostatic parameters in normal men.

Populations that consume a diet rich in marine lipids have been reported to have a lower risk of coronary heart disease. However, some Western population groups with a high fish consumption continue to suffer elevated rates of coronary heart disease. Many of these individuals consume a diet rich in saturated fats in addition to the fish. To examine these possible dietary interactions we fed six healthy men diets that contained two levels of saturated fat (5% and 19% of energy). During 3-week periods the study subjects were given diets with a low-(25% of energy) and high-(39% of energy) fat content with and without inclusion of n-3 polyunsaturated or monounsaturated fatty acids (2% of energy). The effects of the n-3 fatty acids on the principal plasma lipid fractions were similar regardless of the saturated fat intake. Platelet function, as measured by the skin bleeding time, was inhibited when n-3 fatty acids were added to the low saturated-fat diet. In vivo thromboxane A2 production as assessed by urinary metabolites also declined (p < 0.01) during supplementation with n-3 fatty acids to a low-fat diet. Prostacyclin production were reduced on a low-fat diet compared to a high-fat diet regardless of supplementation with n-3 fatty acids. N-3 fatty acids stimulated the synthesis of modest amounts of thromboxane A3 and prostacyclin I3, on both the low and high saturated-fat diets. These studies showed that the effects of eicosapentaenoic and docosahexaenoic acids on platelet and vascular function and eicosanoid production are modulated by the content of saturated fatty acids in the diet.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Brain metabolism in teenagers with attention-deficit hyperactivity disorder.

OBJECTIVES: We sought to obtain and compare values of cerebral glucose metabolism in normal minors and minors with Attention Deficit Hyperactivity Disorder (ADHD). We also sought to confirm our earlier findings of reduced brain metabolism in adults with ADHD, and to examine whether these results might be diagnostically useful. DESIGN: Case-control study. SETTING: Adolescents were recruited to National Institutes of Health Clinical Center/Research Facility through advertisement at local high schools and ADHD organizations. PATIENTS: Subjects were 10 normal adolescents and 10 adolescents with ADHD diagnosed with structured interviews using DSM-III-R criteria. MAIN OUTCOME MEASURES: Positron emission tomography and fludeoxyglucose F18 were used to study cerebral glucose metabolism in minors while they performed an auditory-attention task. RESULTS: Global or absolute measures of metabolism did not statistically differ between groups, although hyperactive girls had a 17.6% lower absolute brain metabolism than normal girls. As compared with the values for the controls, normalized glucose metabolism was significantly reduced in six of 60 specific regions of the brain, including an area of the left anterior frontal lobe (P < .05). Lower metabolism in that specific region of the left anterior frontal lobe was significantly inversely correlated with measures of symptom severity (P < .001-.009, r = -.56 to -.67). CONCLUSIONS: Global or absolute measures of metabolism using positron emission tomography and fludeoxyglucose F18 did not statistically differentiate between normal adolescents with ADHD. Positron emission tomography scans can be performed and are well tolerated by normal teenagers and teenagers with ADHD. The feasibility of normal minors participating in research involving radiation was established.

Adolescent↗
PubMed1993

Nicotine effects on eicosanoid formation and hemostatic function: comparison of transdermal nicotine and cigarette smoking.

OBJECTIVES: The purpose of this study was to examine the possible role of nicotine in enhancing coagulation and to assess the potential cardiovascular toxicity of transdermal nicotine therapy for smoking cessation. BACKGROUND: Cigarette smoking increases the risks of acute coronary events. A likely contributing mechanism is activation of coagulation. The role of nicotine in enhancing coagulability has not been resolved. METHODS: We compared in a crossover study the effects of cigarette smoking, transdermal nicotine and placebo transdermal nicotine, each for 5 days, in 12 healthy smokers. RESULTS: Cigarette smoking increased the urinary excretion of 11-dehydro-thromboxane B2 (reflecting thromboxane A2 generation) and increased plasma concentration of the platelet alpha-granule constituents, platelet factor 4 and beta-thromboglobulin, compared with placebo treatment, indicating in vivo platelet activation. Cigarette smoking was also associated with higher levels of fibrinogen in plasma. Transdermal nicotine produced plasma levels of nicotine in the same range as those during smoking but had no effect on thromboxane A2 metabolite excretion, platelet alpha-granule release or plasma fibrinogen, compared with placebo. Excretion of 2,3-dinor-6-keto-PGF1 alpha (reflecting prostacyclin generation) was not significantly influenced by any treatment. These results suggest that nicotine as such is not responsible for the platelet activation or elevation of plasma fibrinogen seen in smokers. However, we cannot exclude the possibility that intermittent bolus-like dosing of nicotine from cigarettes could have different effects from those produced by continually released transdermal nicotine. Other findings were that cigarette smoking and transdermal nicotine treatment were both associated with a higher white blood cell count compared with the placebo patch condition, suggesting a direct effect of nicotine to increase circulating white cells. Factor VII coagulant activity (VIIc) was significantly lower during cigarette smoking, than during either nicotine or placebo patch conditions. CONCLUSIONS: Transdermal nicotine has less effect on platelet activation and catecholamine release than does cigarette smoking, and its use in smoking cessation treatment of patients with coronary heart disease is likely to be safer than cigarette smoking.

6-Ketoprostaglandin F1 alpha↗
PubMed1993

Biopharmaceutical characterisation of a low-dose (75 mg) controlled-release aspirin formulation.

The release of aspirin from a 75 mg controlled-release formulation, designed to inhibit maximally thromboxane A2 production while sparing stimulated prostacyclin biosynthesis, was characterised in healthy subjects. The calculated in vivo release rate of aspirin matched the design goal of approximately 10 mg h(-1). The C(max) of aspirin associated with the controlled-release formulation was lowered 15-fold relative to a solution formulation of the same dose. The bioavailability of aspirin (based on salicylate concentrations) from the controlled-release formulation was approximately 90% relative to the solution, and drug release was not affected by co-administration of a standard breakfast.

Adolescent↗
PubMed1993

Cellular activation by thromboxane A2 and other eicosanoids.

Thromboxane A2 (TXA2), the major cyclooxygenase (COX) product of arachidonic acid (AA), activates platelets and is a potent vasoconstrictor. The functional importance of this eicosanoid has been demonstrated in syndromes of acute coronary ischaemia. The cellular response to this agonist is tightly regulated. The liberation of AA from membrane phospholipids is conventionally thought to be the rate limiting step in TXA2 biosynthesis. However, the discovery of a second, highly regulated COX gene (COX-2) and the demonstration of product-based inactivation of COX and thromboxane synthase suggest a more complex regulation of TXA2 formation. TXA2 signalling is mediated by a G-protein linked receptor (PGH2/TXA2 receptor) which activates phospholipase C (PLC). Pharmacological studies suggest two distinct binding sites on platelets, but receptor heterogeneity has yet to be documented at a molecular level. The PGH2/TXA2 receptors are linked via a pertussis and cholera toxin-insensitive G-protein which has not been fully characterized, but is thought to belong to the Gq class of G-proteins. The diversity of G-protein alpha subunits, and growing evidence suggesting functional roles for the beta-gamma subunit, support a possible dual signalling mechanism of cellular activation. This may be of particular importance in regulating the response to eicosanoids with contrasting actions. A receptor for prostacyclin (PGI2) has not yet been cloned but biochemical studies suggest that it is linked to the activation of adenylate cyclase via Gs. At least three distinct prostaglandin E receptors have been identified. Desensitization of the cellular responses to the activation of TXA2, PGI2 and PGE receptors have been demonstrated and potential phosphorylation sites in their COOH terminal ends may be important in mediating this effect.

Coronary Disease↗
PubMed1993

Point mutation in the seventh hydrophobic domain of the human thromboxane A2 receptor allows discrimination between agonist and antagonist binding sites.

Thromboxane A2, a potent platelet agonist and vasoconstrictor, exerts its actions via specific G protein-coupled receptors. cDNAs encoding the full length thromboxane receptor have been isolated from human placenta mRNA by reverse transcriptase-polymerase chain reaction. An expression construct, under control of the cytomegalovirus promoter, was introduced into human embryonic kidney 293 cells. Membranes from transfected cells bound the thromboxane antagonist SQ29,548 and the agonist [15-(1 alpha,2 beta(5z)-3 alpha(1E,3S)-4 alpha)]-7-[3-(3-hydroxy-4-(p- iodophenoxy)-1-butenyl)-7-oxabicyclo[2,2,1]hept-2-yl]-5-heptenoic acid) with high affinities, and significantly more receptors were expressed in these cells, compared with platelet preparations. The putative seventh transmembrane segment is highly related in all cloned members of the eicosanoid receptor family and forms a critical portion of the ligand binding pocket for G protein-coupled receptors. Several point mutations in this segment were generated. Binding of SQ29,548 was virtually abolished in cells transfected with all the variant receptor constructs. However, one receptor variant (TxR-W299L), in which a tryptophan at position 299 was substituted for a leucine residue, allowed a definite discrimination between agonist and antagonist binding sites in competition and saturation binding experiments. An antibody directed toward the third intracellular loop of the thromboxane receptor was able to immunoprecipitate native thromboxane receptor in solubilized membranes from human erythroleukemia cells and transfected cells.

Amino Acid Sequence↗
PubMed1992

Increased excretion of leukotriene E4 during aspirin-induced asthma.

The etiology of aspirin-sensitive asthma is unknown, but a plausible hypothesis is that the inhibitory effect of aspirin on the cyclooxygenase enzyme increases formation of bronchoconstrictor leukotrienes via "shunting" of unmetabolized arachidonic acid into metabolism by the 5-lipoxygenase enzyme. The severity and rapidity of bronchospasm that is induced by cyclooxygenase-inhibiting drugs in aspirin-sensitive asthmatics is directly related to the dose and to the potency of the drug to inhibit the cyclooxygenase enzyme. Since increased leukotriene synthesis has recently been shown to occur during allergen-induced asthma, we have examined whether altered leukotriene synthesis correlates with the degree of either cyclooxygenase inhibition or bronchospasm during asthma that is induced by doses of aspirin that range from 30 to 365 mg in individual patients. Excretion of leukotriene E4 was increased by a mean of 361% +/- 76% (p less than 0.05) during aspirin-induced asthma episodes, but the degree of increase for individual patients did not correlate with the degree of bronchospasm or inhibition of platelet thromboxane B2 formation. Thus although the endogenous synthesis of potent bronchoconstrictor leukotrienes increases during aspirin-induced bronchospasm, it appears unlikely that a direct "shunting" of unmetabolized arachidonate into leukotriene synthesis represents the mechanism of aspirin-induced asthma.

Aspirin↗
PubMed1991

Heterogeneity of prostaglandin H2/thromboxane A2 receptors: distinct subtypes mediate vascular smooth muscle contraction and platelet aggregation.

Studies of the hierarchies of agonist and antagonist affinity for the prostaglandin (PG)H2/thromboxane (Tx)A2 receptor have been performed to establish whether distinct receptor subtypes exist in platelets and vascular smooth muscle cells (VSMC). They have yielded conflicting results. The pattern of homologous desensitization of phospholipase C activation and [Ca++i] increase induced by the PGH2/TxA2 agonist U46619 in rat aortic SMC was similar to that previously observed in human platelets: rapid desensitization of both responses followed by a delayed loss of binding sites from the cell membrane. Recently, the pattern of receptor inactivation by the antagonist ligand, GR 32191, has identified two subtypes in platelets. GR 32191 binds reversibly (GRr) to a site that mediates platelet shape change and an increase [Ca++i] and irreversibly (GRirr) to a site linked to phospholipase C activation and aggregation. In contrast to platelets, studies of ligand dissociation only identified GRr sites in rat aortic SMC and GR 32191 failed to inactivate PGH2/TxA2 receptors as detected by the PGH2/TxA2 receptor antagonist, [3H]SQ 29548. Inhibition of U46619-induced contraction of both rat aortic and human saphenous vein was competitive, consistent with the absence of GRirr sites in VSMC. Platelet activating factor, which heterologously desensitizes U46619-evoked phospholipase C activation in platelets, had no such effect in VSMC. The biochemical events attendant to PGH2/TxA2 receptor desensitization are similar in SMC and platelets. However, both the pattern of receptor inactivation by GR 32191 and of heterologous desensitization by PAF, suggest that VSMC lack the receptor subtype that transduces aggregation of platelets.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1991

A prostacyclin analog impairs the response to tissue-type plasminogen activator during coronary thrombolysis: evidence for a pharmacokinetic interaction.

Inhibition of thromboxane (TX) A2 with aspirin enhances the response to coronary thrombolysis. However, experimental evidence suggests that platelet activation during coronary thrombolysis is mediated by a number of agonists, in addition to TXA2. As a consequence, greater benefit would be expected with antiplatelet agents that have a broader spectrum of activity. However, a recent clinical trial, combining tissue plasminogen activator (t-PA) with the prostacyclin analog, iloprost, did not detect such a benefit. To address the mechanism of this response, we compared the effect of iloprost, a stable analog of prostacyclin, with GR32191, a TXA2/prostaglandin endoperoxide receptor antagonist, on the response to i.v. t-PA in a closed chest, canine model of coronary thrombosis. GR32191 reduced the time to reperfusion by 47% (n = 6, P less than .05), consistent with a role for TXA2-mediated platelet activation in impairing thrombolysis. In contrast, iloprost increased the time to reperfusion by 50% (n = 5, P = NS) and in four of nine animals reperfusion failed to occur despite inhibition of platelet aggregation. In a separate series of experiments, steady-state plasma t-PA clearance increased by 38% (407 +/- 49 vs. 294 +/- 42 ml/min; n = 8, P less than .02) during infusion of iloprost and recovered after its withdrawal. This appeared to be a specific effect, as infusion of nitroglycerin at a dose which induced a similar fall in blood pressure altered neither the time to reperfusion nor plasma t-PA. Iloprost impairs the thrombolytic response to t-PA via an increase in the clearance of this agent.

Alprostadil↗
PubMed1991

Human platelet/erythroleukemia cell prostaglandin G/H synthase: cDNA cloning, expression, and gene chromosomal assignment.

Platelets metabolize arachidonic acid to thromboxane A2, a potent platelet aggregator and vasoconstrictor compound. The first step of this transformation is catalyzed by prostaglandin (PG) G/H synthase, a target site for nonsteroidal antiinflammatory drugs. We have isolated the cDNA for both human platelet and human erythroleukemia cell PGG/H synthase using the polymerase chain reaction and conventional screening procedures. The cDNA encoding the full-length protein was expressed in COS-M6 cells. Microsomal fractions from transfected cells produced prostaglandin endoperoxide-derived products which were inhibited by indomethacin and aspirin. Mutagenesis of the serine residue at position 529, the putative aspirin acetylation site, to an asparagine reduced cyclooxygenase activity to barely detectable levels, an effect observed previously with the expressed sheep vesicular gland enzyme. Platelet-derived growth factor and phorbol ester differentially regulated the expression of PGG/H synthase mRNA levels in the megakaryocytic/platelet-like HEL cell line. The PGG/H synthase gene was assigned to chromosome 9 by analysis of a human--hamster somatic hybrid DNA panel. The availability of platelet PGG/H synthase cDNA should enhance our understanding of the important structure/function domains of this protein and its gene regulation.

Amino Acid Sequence↗
PubMed1990

Allergen-stimulated release of thromboxane A2 and leukotriene E4 in humans. Effect of indomethacin.

Allergen-stimulated release of a cyclooxygenase product (thromboxane [TX] A2) and a 5-lipoxygenase product (leukotriene [LT] E4) into the urine was measured in 10 atopic asthmatics undergoing allergen inhalation. Because indomethacin has been reported to increase allergic-stimulated 5-lipoxygenase product formation and to inhibit the late asthmatic response, we determined the effect of indomethacin (50 mg 3 times a day) or placebo on airway and biochemical responses to inhaled allergen in a randomized, blinded study. Urinary levels of the enzymatic metabolite of TXB2, 11-dehydro-TXB2, increased from 585 +/- 330 to 1,500 +/- 250 pg/mg creatinine (mean +/- SEM, p less than 0.05) 2 h after allergen. Urinary LTE4 increased from 190 +/- 37 to 1,100 +/- 400 (p less than 0.05) 2 h after challenge. The urinary levels of these eicosanoids were not elevated during the late response. Indomethacin significantly reduced urinary 11-dehydro-TXB2 levels without affecting the excretion of LTE4 or pulmonary function. Thus, we failed to obtain evidence for enhanced leukotriene formation during allergic stimulation in vivo in the presence of cyclooxygenase inhibition. Furthermore, we conclude that cyclooxygenase products are likely to play only a marginal role in allergic bronchoconstriction.

Adult↗
PubMed1989

Role of thrombin and thromboxane A2 in reocclusion following coronary thrombolysis with tissue-type plasminogen activator.

Reocclusion of the coronary artery occurs after thrombolytic therapy of acute myocardial infarction despite routine use of the anticoagulant heparin. However, heparin is inhibited by platelet activation, which is greatly enhanced in this setting. Consequently, it is unclear whether thrombin induces acute reocclusion. To address this possibility, we examined the effect of argatroban [MCI9038, (2R,4R)-4-methyl-1-[N alpha-(3-methyl-1,2,3,4-tetrahydro-8- quinolinesulfonyl)-L-arginyl]-2-piperidinecarboxylic acid], a specific thrombin inhibitor, on the response to tissue-type plasminogen activator in a closed-chest canine model of coronary thrombosis. MCI9038 prolonged the thrombin time and shortened the time to reperfusion (28 +/- 2 min vs. 59 +/- 7 min in controls; mean +/- SEM, n = 5, P less than 0.01). At the highest dose, 2.5 mg/kg per hr, complete reocclusion was prevented in four of the five experimental animals, whereas reocclusion occurred in all five controls. However, reperfusion was complicated by cycles of decrease flow, which were abolished by the thromboxane A2 antagonist, GR32191. GR32191 at 1 mg/kg combined with MCI9038 at 0.5 mg/kg per hr prevented reocclusion, whereas, at these doses, either drug alone was without effect. In addition, thromboxane A2 biosynthesis, determined as excretion of its metabolite 2,3-dinor-thromboxane B2, was increased after reperfusion at all doses of MCI9038. These data demonstrate that thrombin impairs thrombolysis induced by tissue-type plasminogen activator in vivo and induces acute reocclusion. Furthermore, the response to thrombin inhibition may be impaired by continued formation of thromboxane A2.

Animals↗
PubMed1989

Fish oils in cardiovascular disease.

Although several studies have reported an inverse relationship between the dietary history of fish intake and the prospective incidence of death from coronary heart disease, it is unclear whether these results represent the effects of n-3 fatty acids themselves or whether they merely reflect a more fundamental alteration in diet, such as a reduction in saturated fatty acids. n-3 fatty acids alter platelet eicosanoid formation, replacing arachidonate derived thromboxane (Tx)A2 with the biologically inert TxA3. However, they are a relatively inefficient approach to platelet inhibition. This is evident from results obtained in a model of coronary thrombosis followed by thrombolysis with tissue plasminogen activator (tPA). By contrast, high doses of n-3 fatty acids (15 g day-1) significantly reduced blood pressure in mild hypertensives in a double-blind, controlled study characterized by a prolonged run-in period and adequate follow-up. Fish oils inhibit the vascular proliferative response to injury in a variety of animal models, apparently independently of their effects on lipoprotein metabolism. Recent results imply that they may selectively interfere with the vascular expression of mitogenic peptides.

Arteriosclerosis↗
PubMed1989

Allergen-stimulated release of mediators into sheep bronchoalveolar lavage fluid. Effect of cyclooxygenase inhibition.

Products of arachidonic acid have been implicated as potential mediators of allergic airway responses in sheep and in humans. We therefore measured the release of arachidonate metabolites into sheep bronchoalveolar lavage fluid (BALF) after local instillation of Ascaris antigen, using a highly specific and sensitive approach, gas chromatography-negative ion-chemical ionization mass spectrometry. Allergen instillation caused increases in the levels of the potent bronchoconstrictors prostaglandin (PG) D2 and thromboxane (TX) A2 (as reflected by levels of TXB2) and of their enzymatic metabolites, 9 alpha, 11 beta-PGF2 and 11-dehydro-TXB2, respectively. Potential bronchodilators, PGI2 and PGE2, were also formed in increased amounts. Levels of the 5-lipoxygenase products, leukotriene (LT) B4 and C4, were not significantly increased. Pretreatment of sheep with cyclooxygenase inhibitors was associated with a decrease in the release of cyclooxygenase products and a concomitant increase in the allergen-stimulated release of LTB4 and LTC4. Eicosanoids are formed promptly in vivo in sheep after allergen instillation: inhibition of cyclooxygenase results in augmented generation of leukotrienes in the airways of sensitive sheep in response to antigen challenge.

Allergens↗
PubMed1989

Thromboxane biosynthesis in allergen-induced bronchospasm. Evidence for platelet activation.

To determine if platelet activation occurs after allergen inhalation in atopic asthmatics, we measured two urinary metabolites of the principal cyclooxygenase product of platelets, thromboxane A2 (TxA2), using the sensitive and specific technique of gas chromatography-negative ion, chemical ionization-mass spectrometry. Seven atopic asthmatics underwent allergen challenge after low dose aspirin to suppress platelet thromboxane generation and on placebo days. On placebo days, the urinary levels of 2,3-dinor-TxB2 increased from 76 +/- 22 pg/mg creatinine to 216 +/- 95 after allergen, and 11-dehydro-TxB2 from 396 +/- 98 to 627 +/- 137 (p less than 0.05). Low dose aspirin suppressed excretion of urinary thromboxane metabolites and prevented the rise after allergen inhalation without altering the bronchoconstriction. Excretion of 2,3-dinor-6-keto-PGF1 alpha, a metabolite of prostacyclin, was unaltered by this aspirin regimen. We conclude that platelets are activated after allergen challenge, but that platelet-derived TxA2 is not important in the early bronchoconstrictor response.

6-Ketoprostaglandin F1 alpha↗
PubMed1988

Leukotriene B4 synthesis and neutrophil chemotaxis in chronic granulocytic leukaemia.

A sensitive gas chromatography-mass spectrometric method was used to measure the generation in whole blood of leukotriene B4 (LTB4), a potent stimulator of neutrophil chemotaxis, in eight patients with chronic granulocytic leukaemia (CGL) and 12 healthy controls. LTB4 was detectable in unstimulated samples from all the patients (mean 194 (70 SEM) pg/ml), and the capacity for LTB4 production after stimulation with calcium ionophore (A23187) was similar in patients (32.1 (11) ng/10(6) leucocytes) and controls (38.1 (4) ng/10(6) leucocytes). In response to stimuli which induce neutrophil activation, LTB4 production was significantly greater in the patients than in controls: 35.6 (13) v 13.0 (3) ng/ml, p less than 0.05 (f-met-leu-phe); and 42.4 (16) v 14.7 (4) ng/ml, p less than 0.02 (opsonised zymosan). Anti-IgE stimulated considerably more LTB4 production in patients with CGL than in controls (3.86 (1.6) v 0.83 (0.43) ng/ml; p less than 0.005) and this correlated significantly (p less than 0.05) with the basophil count. Neutrophil chemotaxis to LTB4, however, was significantly impaired in the patients with CGL even at the highest concentration of LTB4 (10(-5) M). Chemotaxis to f-met-leu-phe, phagocytosis, and bacterial killing were normal. Thus although LTB4 synthesis is normal or even enhanced in patients with CGL, specific defects in LTB4-mediated responses may contribute to neutrophil dysfunction in this disease.

Adult↗
PubMed1988

Excretion of prostacyclin and thromboxane A2 metabolites during leg exercise in humans.

Urinary levels of 2,3-dinorthromboxane B2 (Tx-M) and 2,3-dinor-6-ketoprostaglandin F1 alpha (PGI-M), measured by gas chromatography-negative ion-chemical ionization mass spectrometry, accurately reflect in vivo biosynthesis of thromboxane A2 (TxA2) and prostacyclin (PGI2), respectively. Although the basal excretion of Tx-M and PGI-M is adequately documented, no systemic data on the excretion during controlled exercise have been presented. We studied the effect of maximal tolerated exercise (2 h of bicycle ergometry) on the excretion of Tx-M and PGI-M in healthy humans. In addition, their urinary levels of epinephrine (E) and norepinephrine (NE) were analyzed. To address the impact of locally formed adenosine, all subjects were reinvestigated after administration of theophylline. Exercise did not affect the excretion of Tx-M (47 +/- 21 vs. 34 +/- 9 pg/mg creatinine) but increased the excretion of PGI-M (74 +/- 14 vs. 267 +/- 70 pg/mg creatinine; P less than 0.02). Theophylline augmented urinary NE and E but did not significantly change the PGI-M response to exercise. We suggest that the normal cardiovascular eicosanoid response to exercise is a platelet-independent increase in vascular PGI2 formation.

Adult↗