dinoprost and Constriction--Pathologic

Evaluate the effect of the marine lipid fraction of the New Zealand green-lipped mussel (Perna canaliculus) PCSO-524 (Lyprinol/Omega XL), rich in omega-3 fatty acids, on airway inflammation and the bronchoconstrictor response to eucapnic voluntary hyperpnea (EVH) in asthmatics.. Twenty asthmatic subjects, with documented HIB, participated in a placebo controlled double-blind randomized crossover trial. Subjects entered the study on their usual diet and were then placed on 3 weeks of PCSO-524 or placebo supplementation, followed by a 2 week washout period, before crossing over to the alternative diet. Pre- and post-eucapnic voluntary hyperpnea (EVH) pulmonary function, fraction of exhaled nitric oxide (FENO), asthma symptom scores, medication use, exhaled breath condensate (EBC) pH, cysteinyl leukotrienes (cyst-LT), 8-isoprostane and urinary 9α, 11β-prostaglandin (PG)F2 and Clara (CC16) protein concentrations were assessed at the beginning of the trial and at the end of each treatment period.. The PCSO-524 diet significantly reduced (p < 0.05) the maximum fall in post-EVH FEV1 (-8.4 ± 3.2%) compared to usual (-19.3 ± 5.4%) and placebo diet (-22.5 ± 13.7%). Pre- and post- EVH EBC cyst-LT and 8-isoprostane, and urinary 9α, 11β-PGF2 and CC16 concentrations were significantly reduced (p < 0.05) on the PCSO-524 diet compared to the usual and placebo diet. EBC pH and asthma symptom scores were significantly improved (p < 0.05) and rescue medication use significantly reduced (p < 0.05) on the PCSO-524 diet compared to the usual and placebo diet.. PCSO-524 (Lyprinol)/Omega XL) may have beneficial effects in HIB and asthma by serving as a pro-resolving agonist and/or inflammatory antagonist.

Topics: Adrenergic beta-Agonists; Animals; Anti-Asthmatic Agents; Asthma; Biological Products; Biomarkers; Bivalvia; Breath Tests; Bronchitis; Bronchoconstriction; Bronchodilator Agents; Constriction, Pathologic; Cross-Over Studies; Dietary Supplements; Dinoprost; Double-Blind Method; Fatty Acids, Omega-3; Female; Forced Expiratory Volume; Humans; Hyperventilation; Lipids; Male; Medication Adherence; Nitric Oxide; Uteroglobin; Young Adult

Exercise-induced bronchoconstriction (EIB) in the asthmatic child is associated with persistent airway inflammation and poor disease control. EIB could arise partly from airway oxidative stress. Exhaled breath condensate (EBC) levels of 8-isoprostane (IsoP), which is a known marker of oxidative stress, might therefore be helpful for monitoring asthma noninvasively.. We recruited 46 asthmatic children and adolescents 6 to 17 years of age (29 boys), all of whom underwent lung function testing, measurement of the fractional concentration of exhaled nitric oxide (FENO), and collection of EBCs for 8-IsoP measurement before and after exercise challenge. FENO was measured before exercise and 5 min and 20 min after exercise. Spirometry was repeated 1, 5, 10, 15, and 20 min after exercise.. Baseline 8-IsoP levels (but not baseline FENO levels) correlated with the fall in FEV(1) 5 min after exercise (r = - 0.47; p = 0.002). 8-IsoP levels measured after exercise remained unchanged from baseline levels; conversely, FENO levels decreased in parallel with the decline in FEV(1) at 5 min (r = 0.44; p = 0.002). The mean baseline 8-IsoP concentrations were higher in patients with EIB (n = 12) than in those without EIB (n = 34; 44.9 pg/mL [95% confidence interval (CI), 38.3 to 51.5] vs 32.3 pg/mL [95% CI, 27.6 to 37.0], respectively; p < 0.01). No difference was found in the mean baseline FENO between groups (with EIB group: 38.7 ppb; 95% CI, 24.5 to 61.1; without EIB group: 29.1 ppb; 95% CI, 22.0 to 38.4).. Increased 8-IsoP concentrations in EBC samples of asthmatic children and adolescents with EIB suggest a role for oxidative stress in bronchial hyperreactivity.

Topics: Adolescent; Asthma; Biomarkers; Breath Tests; Bronchial Hyperreactivity; Child; Constriction, Pathologic; Dinoprost; Exercise; Exhalation; Female; Humans; Male; Oxidative Stress; Reproducibility of Results; Spirometry

The authors investigated prostacyclin (PGI2) and thromboxane (TX) productions in peripheral venous blood after lower limb revascularization by percutaneous transluminal angioplasty (PTA) versus diagnostic angiography. The purpose of this study was to investigate PGI2/TX imbalance after PTA. This imbalance is of pathophysiologic importance and it is a potential sign of platelet function alteration.. Twenty-five patients requiring PTA were compared with 20 patients undergoing angiography alone from April 2004-December 2005 from a single vascular unit. Patient age range was 42-90 years, and the majority of patients were men. Prostaglandin F2-alpha (PGF2-alpha) and thromboxane B2 (TXB2) were measured sequentially (preprocedure, at 1 hour, and 24 hours after procedure). Differences between postprocedure and preprocedure level were compared statistically between angiography and PTA.. Baseline demographics were distributed equally between the two groups except presence of critical ischemia and ankle brachial pressure index, which were two significant confounders. TXB2 was significantly higher after PTA at 1 hour and 24 hours after PTA (P = .005 and P = .014 respectively), PGF2-alpha was significantly higher 24 hours after PTA only (P = .018) (Mann-Whitney U test).. PGI2/TX balance homeostasis is of significant pathophysiologic importance. The authors found that PTA results in significant PGI2/TX imbalance and shifts more toward increased TX production. This finding is partly suggestive of significant platelet activation. This imbalance in PGI2/TX level may have implications for future failure of PTA. Future research in reducing this platelet activation is recommended.

Topics: Adult; Aged; Aged, 80 and over; Angioplasty; Ankle Brachial Index; Biomarkers; Blood Platelets; Constriction, Pathologic; Dinoprost; England; Epoprostenol; Female; Femoral Artery; Humans; Iliac Artery; Lower Extremity; Male; Middle Aged; Peripheral Arterial Disease; Platelet Activation; Prostaglandins I; Radiography, Interventional; Thromboxane A2; Thromboxane B2; Thromboxanes; Time Factors; Treatment Outcome

The mechanisms through which p38 mitogen-activated protein kinase (p38 MAPK) is involved in smooth muscle contraction remain largely unresolved. We examined the role of p38 MAPK in prostaglandin F(2alpha) (PGF(2alpha))-induced vasoconstriction and in hypoxic pulmonary vasoconstriction (HPV) of rat small intrapulmonary arteries (IPA). The p38 MAPK inhibitors SB-203580 and SB-202190 strongly inhibited PGF(2alpha)-induced vasoconstriction, with IC(50)s of 1.6 and 1.2 microM, whereas the inactive analog SB-202474 was approximately 30-fold less potent. Both transient and sustained phases of HPV were suppressed by SB-203580, but not by SB-202474 (both 2 microM). Western blot analysis revealed that PGF(2alpha) (20 microM) increased phosphorylation of p38 MAPK and of heat shock protein 27 (HSP27), and this was abolished by SB-203580 but not by SB-202474 (both 2 microM). Endothelial denudation or blockade of endothelial nitric oxide (NO) synthase with N(omega)-nitro-L-arginine methyl ester (L-NAME) significantly suppressed the relaxation of PGF(2alpha)-constricted IPA by SB-203580, but not by SB-202474. Similarly, the inhibition of HPV by SB-203580 was prevented by prior treatment with L-NAME. SB-203580 (2 microM), but not SB-202474, enhanced relaxation-induced by the NO donor S-nitroso-N-acetylpenicillamine (SNAP) in endothelium-denuded IPA constricted with PGF(2alpha). In alpha-toxin-permeabilized IPA, SB-203580-induced relaxation occurred in the presence but not the absence of the NO donor sodium nitroprusside (SNP); SB-202474 was without effect even in the presence of SNP. In intact IPA, neither PGF(2alpha)- nor SNAP-mediated changes in cytosolic free Ca(2+) were affected by SB-203580. We conclude that p38 MAPK contributes to PGF(2alpha)- and hypoxia-induced constriction of rat IPA primarily by antagonizing the underlying Ca(2+)-desensitizing actions of NO.

Topics: Animals; Calcium; Calcium Signaling; Constriction, Pathologic; Dinoprost; Enzyme Inhibitors; Heat-Shock Proteins; HSP27 Heat-Shock Proteins; Hypoxia; Male; Muscle Contraction; Neoplasm Proteins; Nitric Oxide; Nitric Oxide Synthase Type III; Organ Culture Techniques; Oxytocics; p38 Mitogen-Activated Protein Kinases; Phosphorylation; Pulmonary Artery; Rats; Rats, Wistar

Topics: Animals; Bradykinin; Cold Temperature; Constriction, Pathologic; Dilatation, Pathologic; Dinoprost; Endothelin-1; Endothelin-3; Male; Middle Cerebral Artery; Nitroprusside; Parietal Lobe; Rats

Inhalation of cigarette smoke induces a biphasic bronchoconstriction in guinea pigs: the first phase is induced by a combination of cholinergic reflex and tachykinins, whereas the second phase involves cyclooxygenase metabolites (J.-L. Hong, I. W. Rodger, and L.-Y. Lee. J. Appl. Physiol. 78: 2260-2266, 1995). This study was carried out to further determine the causative agents in the smoke and the types of prostanoid receptors and endogenous prostanoids mediating the bronchoconstriction. Inhalation of 10 ml of high-nicotine cigarette smoke consistently elicited the biphasic bronchoconstriction in anesthetized and artificially ventilated guinea pigs. Pretreatment with hexamethonium (10 mg/kg iv) significantly reduced the first-phase bronchoconstriction but did not have any measurable effect on the second-phase response. In sharp contrast, gas-phase smoke did not elicit any bronchoconstrictive effect. Furthermore, when the animals were challenged with low-nicotine cigarette smoke, only a single second-phase response was evoked, accompanied by increases in thromboxane (Tx) B2 (a stable metabolite of TxA2), prostaglandin (PG) D2, PGF2 alpha in the bronchoalveolar lavage fluid. The bronchoconstrictive response induced by low-nicotine smoke was completely prevented by pretreatment with SQ-29548 (0.3 mg/kg iv), a TxA2-receptor antagonist. These results indicate that 1) nicotine is the primary causative agent responsible for the first-phase bronchoconstriction and 2) nonnicotine smoke particulates evoke the release of TxA2, PGD2, and PGF2 alpha, which act on TxA2 receptors on airway smooth muscles and induce the second-phase response to cigarette smoke.

Topics: Air Pressure; Animals; Bridged Bicyclo Compounds, Heterocyclic; Bronchial Diseases; Bronchoalveolar Lavage Fluid; Cholinergic Antagonists; Constriction, Pathologic; Dinoprost; Fatty Acids, Unsaturated; Guinea Pigs; Hemodynamics; Hexamethonium; Hydrazines; Male; Nicotine; Nicotinic Agonists; Receptors, Thromboxane; Smoke; Smoking

Hypoxia alters the responsiveness to endogenous substances of cerebral arteries, possibly resulting in the modulation of blood supply to ischemic brain regions. The present study was undertaken to analyze the mechanism of potentiation by hypoxia of angiotensin II-induced cerebroarterial contractions.. Monkey and dog cerebral arterial strips with endothelium were suspended for isometric tension recording in Ringer-Locke solution aerated with 95% O2-5% CO2 (partial pressure, 570-600 mm Hg) or 95% N2-5% CO2 (approximately 10 mm Hg).. Contractions induced by angiotensin II and substance P were potentiated by exposure to hypoxia, whereas contractile responses to prostaglandin F2 alpha were not influenced. Treatment with cyclooxygenase inhibitors abolished the peptide-induced contraction but did not alter the prostaglandin F2 alpha-induced contraction. Relaxations induced by arachidonic acid were suppressed by indomethacin and hypoxia, whereas those caused by a prostaglandin I2 analogue were unaffected.. The potentiation by hypoxia of cerebroarterial contractions caused by angiotensin II and substance P appears to be due to an interference with the synthesis of prostaglandin I2 from arachidonic acid and a resultant increase in the production of vasoconstrictor prostaglandins.

Topics: Angiotensin II; Animals; Cerebral Arteries; Constriction, Pathologic; Cyclooxygenase Inhibitors; Dinoprost; Disease Models, Animal; Dogs; Endothelium, Vascular; Female; Hypoxia; Macaca; Male; Substance P

To investigate whether bronchial C-fiber stimulation induced by capsaicin inhalation evokes nonadrenergic inhibitory (NAI) system bronchodilation, we studied partial and maximal expiratory flow-volume (PEFV and MEFV) curves in 5 normal subjects after inhalation of oxitropium bromide and propranolol. PGF2 alpha (1 mg/ml inhaled for 5 min) was administered to induce bronchoconstriction. Then aerosolized capsaicin was inhaled (2.4 x 10(-9) mol) to stimulate bronchial C-fibers. PGF2 alpha produced significant bronchoconstriction; FEV1 and flow during a PEFV curve at 30% forced vital capacity (V30p) decreased over a 15-min period. Capsaicin induced significant bronchodilation; V30p increased for 2 to 6 min (0.001 less than p less than 0.02), and FEV1 increased for 2 to 4 min (p less than 0.05) when compared with saline-ethanol (vehicle of capsaicin) inhalation. After treatment with the ganglionic blocking agent hexamethonium, the significant bronchodilator response disappeared. These results suggest that the NAI system has a distinct bronchodilator action in human subjects in vivo, and that the bronchial C-fiber receptors may be involved in the reflex pathway for NAI system bronchodilation in humans.

Topics: Adult; Bronchi; Bronchodilator Agents; Capsaicin; Constriction, Pathologic; Dinoprost; Forced Expiratory Volume; Humans; Nerve Fibers; Nervous System Physiological Phenomena; Receptors, Adrenergic; Receptors, Muscarinic; Reference Values

The porcine pulmonary vascular and airway responses to exogenous 5-hydroxytryptamine (5-HT), norepinephrine, prostaglandin F2 alpha (PGF2 alpha), and angiotensin II were evaluated before and after ketanserin, a 5-HT2 receptor antagonist. Ketanserin blocked the 5-HT-induced increases in airway and pulmonary artery pressures, whereas the increases in airway and pulmonary artery pressures caused by norepinephrine, PGF2 alpha, or angiotensin II were not significantly modified by ketanserin, indicating a relatively high degree of specificity for 5-HT2 receptors. The role of endogenous 5-HT in mediating endotoxin-induced respiratory failure was evaluated by treating pigs with ketanserin. Escherichia coli endotoxin (055-B5) was infused intravenously into anesthetized 10- to 14-wk-old pigs at 5 micrograms/kg the first h, followed by 2 micrograms/kg/h for 3.5 h. Ketanserin was infused at 300 micrograms/kg before endotoxin plus 67 micrograms/kg/h during endotoxemia. During Phase 1 (i.e., 0 to 2 h), the endotoxin-induced increases in pulmonary vascular resistance and room air alveolar-arterial oxygen difference and the decreased cardiac index and lung dynamic compliance were not significantly modified by ketanserin. However, during Phase 2 (i.e., 2 to 4.5 h) endotoxemia, ketanserin attenuated the endotoxin-induced pulmonary hypertension and the increases in pulmonary vascular resistance, alveolar dead space ventilation, and alveolar-arterial oxygen difference. Ketanserin also attenuated the Phase 2 bronchoconstriction and the decreased cardiac index, but did not modify the endotoxin-induced increase in alveolar-capillary permeability. These results indicate that 5-HT plays little or no role in mediating the early (i.e., less than 2 h) response to endotoxin.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acute Disease; Angiotensin II; Animals; Bronchi; Constriction, Pathologic; Dinoprost; Disease Models, Animal; Dose-Response Relationship, Drug; Endotoxins; Escherichia coli; Ketanserin; Norepinephrine; Prostaglandins F; Pulmonary Artery; Pulmonary Veins; Respiratory Insufficiency; Serotonin; Swine; Swine Diseases; Vascular Resistance