Inflammation induced changes in arachidonic acid metabolism in cat LES circular muscle

2005 ◽  
Vol 288 (4) ◽  
pp. G787-G797 ◽  
Author(s):  
Ling Cheng ◽  
Weibiao Cao ◽  
Jose Behar ◽  
Piero Biancani ◽  
Karen M. Harnett
Keyword(s):  
Arachidonic Acid ◽  
Circular Muscle ◽  
Arachidonic Acid Metabolism ◽  
Acid Metabolites ◽  
Esophageal Sphincter ◽  
Cat Model ◽  
Induced Changes

Myogenic lower esophageal sphincter (LES) tone is maintained by arachidonic acid metabolites, such as PGF2α and thromboxane A2/B2. Experimental esophagitis in cat reduces LES in vivo pressure and in vitro tone. Because IL-1β may mediate esophagitis-associated reduction in ACh release in esophagus, we examined whether IL-1β may also play a role in esophagitis-induced reduction of LES tone. A cat model of experimental esophagitis was obtained by repeated esophageal perfusion with HCl (Biancani P, Barwick K, Selling J, and McCallum R. Gastreonterology 87: 8–16, 1984 and Sohn UD, Harnett KM, Cao W, Rich H, Kim N, Behar J, and Biancani P. J Pharmacol Exp Ther 283: 1293–1304, 1997.). LES circular muscle strips were examined in muscle chambers as previously described (Biancani P, Billett G, Hillemeier C, Nissenshon M, Rhim BY, Sweczack S, and Behar J. Gastroenterology 103: 1199–1206, 1992). Levels of inflammatory mediators were measured. IL-1β levels were higher in esophagitis than in normal LES. IL-1β reduced normal LES tone, and the reduction was reversed by catalase, suggesting a role of H2O2. This was confirmed by IL-1β-induced production of H2O2 in normal LES and elevated H2O2 levels in esophagitis. H2O2 by itself is sufficient to explain the changes that occur in the muscle, reducing its ability to contract. H2O2 increased PGE2 in normal LES, and PGE2 levels were elevated in esophagitis LES, whereas PGF2α levels were unchanged. H2O2 also increased levels of 8-isoprostanes, stable prostaglandin-like compounds formed by free radical-induced peroxidation of arachidonic acid, and 8-isoprostane levels were elevated in esophagitis. The PGF2α analog 8-iso-PGF2α caused little contraction of LES strips but reduced PGF2α binding and contraction of normal LES. In esophagitis, PGF2α binding and contraction were reduced in LES, suggesting that isoprostanes may contribute to reduction in tone in esophagitis. The data suggest that, in esophagitis, IL-1β causes production of H2O2. H2O2 increases PGE2, which relaxes the LES, and 8-iso-F2α, which blocks PGF2α-mediated contraction.

Group I secreted PLA2and arachidonic acid metabolites in the maintenance of cat LES tone

1999 ◽  
Vol 277 (3) ◽  
pp. G585-G598 ◽  
Author(s):  
W. B. Cao ◽  
K. M. Harnett ◽  
Q. Chen ◽  
M. K. Jain ◽  
J. Behar ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Smooth Muscle ◽  
G Proteins ◽  
Circular Muscle ◽  
Group I ◽  
Gtpγs Binding ◽  
Acid Metabolites ◽  
Esophageal Sphincter

Spontaneous tone of in vitro lower esophageal sphincter (LES) circular muscle is associated with elevated levels of arachidonic acid (AA), PGF2α, and increased [35S]guanosine 5′- O-(3-thiotriphosphate) (GTPγS) binding to Gq-, Gi3-, and Gi1/i2-like G proteins. Tone and AA levels were reduced by inhibitors of a pancreatic-like (group I) secreted phospholipase A2(sPLA2), by the cyclooxygenase inhibitor indomethacin, and by the thromboxane A2antagonist SQ-29548. In addition, pertussis toxin (PTX) reduced LES tone, confirming a role of PTX-sensitive G proteins in maintenance of LES tone. PGF2αcontracted LES smooth muscle (strips and cells) and increased [35S]GTPγS binding to Gqand Gi3in solubilized LES circular muscle membranes. PGF2α-induced contraction of LES permeable muscle cells was inhibited by Gqand Gi3but not by Gi1/i2and Goantibodies. The thromboxane A2analog U-46619 contracted LES smooth muscle and increased Gqbinding. U-46619-induced contraction was inhibited by Gqbut not by Gi3, Gi1/i2, and Goantibodies. LES tone and [35S]GTPγS binding were significantly reduced by indomethacin. We conclude that group I sPLA2may mediate “spontaneous” LES tone by producing AA, which is metabolized to PGF2αand thromboxane A2. These AA metabolites activate receptors linked to Gi3and Gqto maintain LES contraction.

In vivo and in vitro influence of human recombinant hemoglobin on esophageal function

1995 ◽  
Vol 268 (3) ◽  
pp. G443-G450 ◽  
Author(s):  
S. Chakder ◽  
G. J. Rosenthal ◽  
S. Rattan
Keyword(s):  
Oxygen Carrier ◽  
Electrical Field Stimulation ◽  
Esophageal Peristalsis ◽  
Esophageal Function ◽  
Significant Impairment ◽  
Esophageal Sphincter ◽  
Peristaltic Contractions

The purpose of the present investigation was to examine the influence of a nitric oxide scavenger, hemoglobin (Hb), on esophageal function. Intraluminal pressures of anesthetized opossums were recorded from lower esophageal sphincter (LES) and 1, 5, and 9 cm above the LES. The influence of a representative Hb-based oxygen carrier was examined on swallowing-induced esophageal peristalsis and LES relaxation. In in vitro studies, LES relaxation and esophageal peristaltic contractions were induced by the activation of nonadrenergic noncholinergic (NANC) neurons by electrical field stimulation (EFS). Hb caused significant impairment in swallowing- and EFS-induced LES relaxation and a significant increase in the speed of esophageal peristalsis. In some experiments, swallowing caused simultaneous contractions in the esophagus following Hb administration. Although Hb completely blocked LES relaxation by NO and significantly attenuated that by NANC nerve stimulation, it had no significant effect on isoproterenol-induced LES relaxations. The data support the role of NO in LES relaxation and esophageal peristalsis. This esophageal model may be important in understanding the influence of NO inhibitors and scavengers in gastrointestinal motility.

Role of endothelial cells in regulating hemoglobin-induced changes in lymphatic pumping

1992 ◽  
Vol 263 (6) ◽  
pp. H1880-H1887 ◽  
Author(s):  
R. M. Elias ◽  
J. Eisenhoffer ◽  
M. G. Johnston
Keyword(s):  
Endothelial Cells ◽  
Smooth Muscle ◽  
Inhibitory Effect ◽  
Direct Inhibitory Effect ◽  
Induced Changes ◽  
Lymphatic Pumping ◽  
Pumping Activity

Studies with a sheep isolated duct preparation in vivo demonstrated that the route of administration of hemoglobin was important in demonstrating its inhibitory effect on lymphatic pumping. With autologous oxyhemoglobin administered intravenously (final plasma concentration 5 x 10(-5) M), pumping was not inhibited. However, the addition of oxyhemoglobin (5 x 10(-5) M) into the reservoir (lumen of the duct) resulted in > 95% inhibition of pumping. The extraluminal administration of oxyhemoglobin (10(-5) M) to bovine mesenteric lymphatics in vitro resulted in a 40% inhibition of pumping, whereas the introduction of oxyhemoglobin (10(-5) M) into the lumen of the vessels suppressed pumping 95%. In vessels mechanically denuded of endothelium, intraluminal oxyhemoglobin inhibited pumping 50%. These results suggested that oxyhemoglobin depressed pumping through an effect on both smooth muscle and endothelium. Once pumping was inhibited with oxyhemoglobin administration, stimulation of the duct with elevations in transmural pressure restored pumping activity when endothelial cells were present. However, in the absence of endothelium, pumping decreased with increases in distending pressures. We conclude that oxyhemoglobin has a direct inhibitory effect on lymphatic smooth muscle. The ability of oxyhemoglobin to alter the pressure range over which the lymph pump operates appears to be dependent on an intact endothelium.

scholarly journals Prostacyclin as a potent effector of adipose-cell differentiation

1989 ◽  
Vol 257 (2) ◽  
pp. 399-405 ◽  
Author(s):  
R Négrel ◽  
D Gaillard ◽  
G Ailhaud
Keyword(s):  
Arachidonic Acid ◽  
Cyclic Amp ◽  
Critical Role ◽  
Terminal Differentiation ◽  
Prostaglandin F2 Alpha ◽  
Adipogenic Effect ◽  
Adipose Cells

The terminal differentiation of Ob1771 pre-adipose cells induced by arachidonic acid in serum-free hormone-supplemented medium containing insulin, transferrin, growth hormone, tri-iodothyronine and fetuin (5F medium) was strongly diminished in the presence of inhibitors of prostaglandin synthesis, namely aspirin or indomethacin. Carbaprostacyclin, a stable analogue of prostacyclin (prostaglandin I2) known to be synthesized by pre-adipocytes and adipocytes, behaved as an efficient activator of cyclic AMP production and was able, when added to 5F medium, to mimic the adipogenic effect of arachidonic acid. Prostaglandins E2, F2 alpha and D2, unable to affect the cyclic AMP production, failed to substitute for carbaprostacyclin. However, prostaglandin F2 alpha, which is another metabolite of arachidonic acid in pre-adipose and adipose cells, able to promote inositol phospholipid breakdown and protein kinase C activation, potentiated the adipogenic effect of carbaprostacyclin. In addition, carbaprostacyclin enhanced both a limited proliferation and terminal differentiation of adipose precursor cells isolated from rodent and human adipose tissues maintained in primary culture. These results demonstrate the critical role of prostacyclin and prostaglandin F2 alpha on adipose conversion in vitro and suggest a paracrine/autocrine role of both prostanoids in the development of adipose tissue in vivo.

Platelet inhibition by aspirin is diminished in patients during carotid surgery: a form of transient aspirin resistance?

2004 ◽  
Vol 92 (07) ◽  
pp. 89-96 ◽  
Author(s):  
David Payne ◽  
Chris Jones ◽  
Paul Hayes ◽  
Sally Webster ◽  
A. Naylor ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Platelet Rich Plasma ◽  
Platelet Inhibition ◽  
Aspirin Resistance ◽  
Arachidonic Acid Metabolism ◽  
Significant Rise ◽  
Control Group

SummaryThe majority of patients who suffer peri-operative thromboembolic complication while undergoing vascular procedures do so despite taking aspirin. This study examined the antiplatelet effect of aspirin during surgery in patients undergoing carotid endarterectomy (CEA). Fifty patients undergoing CEA were standardised to 150 mg aspirin daily for ≥2 weeks. Platelet aggregation in response to arachidonic acid (AA) was measured in platelet rich plasma prepared from blood taken prior to, during, and at the end of surgery. Spontaneous platelet aggregation was also studied, as was the role of physiological agonists (ADP, collagen, thrombin, and epinephrine) in mediating the in vivo and in vitro responses to AA. Eighteen patients undergoing leg angioplasty, also on 150 mg aspirin, without general anaesthesia, served as a control group. In the CEA patients aggregation induced by AA (5 mM) increased significantly from 7.6 ± 5.5% pre-surgery to 50.8 ± 29.5% at the end of surgery (p <0.0001). Aggregation to AA was even greater in samples taken mid-surgery from a sub-set of patients (73.8 ± 7.2%; p = 0.0001), but fell to 45.9 ± 7.4% by the end of surgery. The increased aggregation in response to AA was not due to intra-operative release of physiological platelet agonists since addition of agents that block/neutralise the effects of ADP (apyrase; 4 µg/ml), thrombin (hirudin; 10 units/ml), or epinephrine (yohimbine; 10 µM/l) to the samples taken at the end of surgery did not block the increased aggregation.The patients undergoing angioplasty also showed a significant rise in the response to AA (5 mM), from 5.6 ± 5.5% pre-angioplasty to 32.4 ± 24.9% at the end of the procedure (p <0.0001), which fell significantly to 11.0 ± 8.1% 4 hours later. The antiplatelet activity of aspirin, mediated by blockade of platelet arachidonic acid metabolism, diminished significantly during surgery, but was partially restored by the end of the procedure without additional aspirin treatment.This rapidly inducible and transient effect may explain why some patients undergoing cardiovascular surgery remain at risk of peri-operative stroke and myocardial infarction.

IL-1β signaling in cat lower esophageal sphincter circular muscle

2006 ◽  
Vol 291 (4) ◽  
pp. G672-G680 ◽  
Author(s):  
Weibiao Cao ◽  
Ling Cheng ◽  
Jose Behar ◽  
Piero Biancani ◽  
Karen M. Harnett
Keyword(s):  
Lower Esophageal Sphincter ◽  
P38 Mapk ◽  
Circular Muscle ◽  
Circular Smooth Muscle ◽  
Sequential Activation ◽  
Cox 2 ◽  
Esophageal Sphincter ◽  
Sb 203580

In a cat model of acute experimental esophagitis, resting in vivo lower esophageal sphincter (LES) pressure and in vitro tone are lower than in normal LES, and the LES circular smooth muscle layer contains elevated levels of IL-1β that decrease the LES tone of normal cats. We now examined the mechanisms of IL-1β-induced reduction in LES tone. IL-1β significantly reduced acetylcholine-induced Ca2+ release in Ca2+-free medium, and this effect was partially reversed by catalase, demonstrating a role of H2O2 in these changes. IL-1β significantly increased the production of H2O2, and the increase was blocked by the p38 MAPK inhibitor SB-203580, by the cytosolic phospholipase A2 (cPLA2) inhibitor AACOCF3, and by the NADPH oxidase inhibitor apocynin, but not by the MEK1 inhibitor PD-98059. IL-1β significantly increased the phosphorylation of p38 MAPK and cPLA2. IL-1β-induced cPLA2 phosphorylation was blocked by SB-203580 but not by AACOCF3, suggesting sequential activation of p38 MAPK-phosphorylating cPLA2. The IL-1β-induced reduction in LES tone was partially reversed by AACOCF3 and by the Ca2+-insensitive PLA2 inhibitor bromoenol lactone (BEL). IL-1β significantly increased cyclooxygenase (COX)-2 and PGE2 levels. The increase in PGE2 was blocked by SB-203580, AACOCF3, BEL, and the COX-2 inhibitor NS-398 but not by PD-98059 or the COX-1 inhibitor valeryl salicylate. The data suggested that IL-1β reduces LES tone by producing H2O2, which may affect Ca2+-release mechanisms and increase the synthesis of COX-2 and PGE2. Both H2O2 and PGE2 production depend on sequential activation of p38 MAPK and cPLA2. cPLA2 activates NADPH oxidases, producing H2O2, and may produce arachidonic acid, converted to PGE2 via COX-2.

Effects of kinins on isolated blood vessels. Role of endothelium

1982 ◽  
Vol 60 (12) ◽  
pp. 1580-1583 ◽  
Author(s):  
D. Regoli ◽  
J. Mizrahi ◽  
P. D'Orléans-Juste ◽  
S. Caranikas
Keyword(s):  
Arachidonic Acid ◽  
Carotid Artery ◽  
Common Carotid Artery ◽  
Smooth Muscles ◽  
Rabbit Aorta ◽  
Arachidonic Acid Metabolism ◽  
Arachidonic Acid Cascade ◽  
Vascular Smooth Muscles ◽  
Acid Metabolites

Bradykinin (BK) and des-Arg9-BK were used to determine whether the stimulatory and inhibitory actions of the kinins in various isolated vessels require the presence of endothelium and may be mediated by arachidonic acid metabolites. It was found that the presence of intact endothelium is required only for the relaxation of the dog common carotid artery in response to bradykinin. Stimulatory actions of both BK and des-Arg9-BK in arterial (rabbit aorta) and venous (rabbit jugular and mesenteric vein) smooth muscle do not require the presence of endothelium. Inhibition of the arachidonic acid cascade at various levels affects the relaxing action of acetylcholine (rabbit aorta and dog common carotid artery) while being inactive against both the relaxing (dog common carotid artery) and contractile actions (rabbit aorta, rabbit jugular and mesenteric veins) of bradykinin and des-Arg9-BK. Inhibitors of the arachidonic acid cascade also do not affect the inhibitory action of isopropylnoradrenaline on the rabbit aorta. The present results indicate that stimulant actions of kinins in isolated vascular smooth muscles do not require the presence of endothelium. Endothelium is required for the inhibitory actions of acetylcholine and bradykinin but not for that of isopropylnoradrenaline on the dog carotid artery. Moreover, the inhibition of arachidonic acid metabolism only affects the response of isolated vessels to acetylcholine. The present results suggest that several mechanisms may be involved in the inhibition of vascular tone by vasodilators.

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