Cyclooxygenase inhibitor blocks rebound response after NO inhalation in an endotoxin model

2003 ◽  
Vol 284 (1) ◽  
pp. H290-H298 ◽  
Author(s):  
Luni Chen ◽  
Hao He ◽  
Enrique Fernandez Mondejar ◽  
Göran Hedenstierna
Keyword(s):  
Plasma Concentrations ◽  
Blood Gases ◽  
Control Group ◽  
Hemodynamic Parameters ◽  
Mechanically Ventilated ◽  
Cox Inhibitor ◽  
Group A ◽  
Cox 2 ◽  
Cox 1

This study addressed the possible role of cyclooxygenase (COX) and its products in the rebound response to inhaled nitric oxide (INO). Anesthetized, mechanically ventilated piglets were exposed to endotoxin alone, endotoxin combined with INO, or endotoxin with INO plus the COX inhibitor diclofenac (3 mg/kg iv) ( n = 8 piglets/group). A control group of healthy pigs ( n = 6) was also studied. Measurements were made of blood gases, hemodynamic parameters, lung tissue COX expression, and plasma concentrations of thromboxane B2 (TxB2), PGF2α, and 6-keto-PGF1α. Endotoxin increased lung inducible COX (COX-2) expression and circulating prostanoids concentrations. Inhalation of NO during endotoxemia increased the constitutive COX (COX-1) expression, and the circulating TxB2 and PGF2α increased further after INO withdrawal. The combination of COX inhibitor with INO blocked all these changes and eliminated the rebound reaction to INO withdrawal, which otherwise was seen in endotoxemic piglets given INO only. We conclude that the rebound response to INO discontinuation is related to COX products.

Endothelial COX-1 and -2 differentially affect reactivity of MVB in portal hypertensive rats

2002 ◽  
Vol 283 (3) ◽  
pp. G587-G594 ◽  
Author(s):  
M. A. Potenza ◽  
O. A. Botrugno ◽  
M. A. De Salvia ◽  
G. Lerro ◽  
C. Nacci ◽  
...  
Keyword(s):  
Portal Hypertension ◽  
Hypertensive Rats ◽  
Mesenteric Blood Flow ◽  
Western Blots ◽  
Vascular Bed ◽  
Cox Inhibitor ◽  
Mesenteric Vascular Bed ◽  
Cox 2 ◽  
Cox 1

Expression of constitutive and inducible cyclooxygenase (COX-1 and COX-2, respectively) and the role of prostanoids were investigated in the aorta and mesenteric vascular bed (MVB) from the portal vein-ligated rat (PVL) as a model of portal hypertension. Functional experiments were carried out in MVB from PVL and sham-operated rats in the absence or presence of the nonselective COX inhibitor indomethacin or the selective inhibitors of COX-1 (SC-560) or COX-2 (NS-398). Western blots of COX-1 and COX-2 proteins were evaluated in aorta and MVB, and PGI2 production by enzyme immunoassay of 6-keto-PGF1α was evaluated in the aorta. In the presence of functional endothelium, decreased contraction to norepinephrine (NE) and increased vasodilatation to ACh were observed in MVB from PVL. Exposure of MVB to indomethacin, SC-560, or NS-398 reversed the hyporeactivity to NE and the increased endothelial vasodilatation to ACh in PVL, with NS-398 being more potent than the other two inhibitors. Upregulation of COX-1 and COX-2 expressions was detected in aorta and MVB from PVL portal hypertensive rats, and increased production of 6-keto-PGF1α was observed in aorta from portal hypertensive rats. These results suggest that generation of endothelial vasodilator prostanoids, from COX-1 and COX-2 isoforms, accounts for the increased mesenteric blood flow in portal hypertension.

scholarly journals ChTX induces oscillatory contraction in guinea pig trachea: role of cyclooxygenase-2 and PGE2

2003 ◽  
Vol 284 (6) ◽  
pp. L1045-L1054 ◽  
Author(s):  
Yukihiro Yagi ◽  
Masayoshi Kuwahara ◽  
Hirokazu Tsubone
Keyword(s):  
Guinea Pig ◽  
Prostaglandin E ◽  
Receptor Subtype ◽  
Phasic Contraction ◽  
Oscillatory Frequency ◽  
Cox Inhibitor ◽  
The Mean ◽  
Cox 2 ◽  
Cox 1

We examined the possible role of cyclooxygenase (COX) in charybdotoxin (ChTX)-induced oscillatory contraction in guinea pig trachea. Involvement of prostaglandin E2 (PGE2) in ChTX-induced oscillatory contraction was also investigated. ChTX (100 nM) induced oscillatory contraction in guinea pig trachea. The mean oscillatory frequency induced by ChTX was 10.7 ± 0.8 counts/h. Maximum and minimum tensions within ChTX-induced oscillatory contractions were 68.4 ± 1.8 and 14.3 ± 1.7% compared with K+ (72.7 mM) contractions. ChTX-induced oscillatory contraction was completely inhibited by indomethacin, a nonselective COX inhibitor. Valeryl salicylate, a selective COX-1 inhibitor, did not significantly inhibit this contraction, whereas N-(2-cyclohexyloxy-4-nitro-phenyl)-methanesulfonamide, a selective COX-2 inhibitor, abolished this contraction. Exogenously applied arachidonic acid enhanced ChTX-induced oscillatory contraction. SC-51322, a selective PGE receptor subtype EP1 antagonist, significantly inhibited ChTX-induced oscillatory contraction. Exogenously applied PGE2 induced only a slight phasic contraction in guinea pig trachea, but PGE2 induced strong oscillatory contraction after pretreatment with indomethacin and ChTX. Moreover, ChTX time-dependently stimulated PGE2 generation. These results suggest that ChTX specifically activates COX-2 and stimulates PGE2 production and that ChTX-induced oscillatory contraction in guinea pig trachea is mediated by activation of EP1 receptor.

Cyclooxygenase-2 plays a significant role in regulating the tone of the fetal lamb ductus arteriosus

1999 ◽  
Vol 276 (3) ◽  
pp. R913-R921 ◽  
Author(s):  
Ronald I. Clyman ◽  
Pierre Hardy ◽  
Nahid Waleh ◽  
Yao Qi Chen ◽  
Françoise Mauray ◽  
...  
Keyword(s):  
Significant Role ◽  
Ductus Arteriosus ◽  
Late Gestation ◽  
Relative Contribution ◽  
Cox Inhibitor ◽  
Fetal Lamb ◽  
Cox 2 ◽  
Cox 2 Inhibitors ◽  
Cox 1

Nonselective cyclooxygenase (COX) inhibitors are potent tocolytic agents but have adverse effects on the fetal ductus arteriosus. We hypothesized that COX-2 inhibitors may not affect the ductus if the predominant COX isoform is COX-1. To examine this hypothesis, we used ductus arteriosus obtained from late-gestation fetal lambs. In contrast to our hypothesis, fetal lamb ductus arteriosus expressed both COX-1- and COX-2-immunoreactive protein (by Western analysis). Although COX-1 was found in both endothelial and smooth muscle cells, COX-2 was found only in the endothelial cells lining the ductus lumen (by immunohistochemistry). The relative contribution of COX-1 and COX-2 to PGE2 synthesis was consistent with the immunohistochemical results: in the intact ductus, PGE2 formation was catalyzed by both COX-1 and COX-2 in equivalent proportions; in the endothelium-denuded ductus, COX-2 no longer played a significant role in PGE2 synthesis. NS-398, a selective inhibitor of COX-2, was 66% as effective as the selective COX-1 inhibitor valeryl salicylate and the nonselective COX inhibitor indomethacin in causing contraction of the ductus in vitro. At this time, caution should be used when recommending COX-2 inhibitors for use in pregnant women.

scholarly journals Role of cyclooxygenase isoforms in prostacyclin biosynthesis and murine prehepatic portal hypertension

2008 ◽  
Vol 295 (5) ◽  
pp. G953-G964 ◽  
Author(s):  
N. J. Skill ◽  
N. G. Theodorakis ◽  
Y. N. Wang ◽  
J. M. Wu ◽  
E. M. Redmond ◽  
...  
Keyword(s):  
Portal Hypertension ◽  
The United States ◽  
Portal Vein Ligation ◽  
Wild Type ◽  
Sham Surgery ◽  
Cox 2 ◽  
Hemodynamic Measurements ◽  
Cyclooxygenase Isoforms ◽  
Cox 1

Portal hypertension (PHT) is a common complication of liver cirrhosis and significantly increases morbidity and mortality. Abrogation of PHT using NSAIDs has demonstrated that prostacyclin (PGI2), a direct downstream metabolic product of cyclooxygenase (COX) activity, is an important mediator in the development of experimental and clinical PHT. However, the role of COX isoforms in PGI2 biosynthesis and PHT is not fully understood. Prehepatic PHT was induced by portal vein ligation (PVL) in wild-type, COX-1−/−, and COX-2−/− mice treated with and without COX-2 (NS398) or COX-1 (SC560) inhibitors. Hemodynamic measurements and PGI2 biosynthesis were determined 1–7 days after PVL or sham surgery. Gene deletion or pharmacological inhibition of COX-1 or COX-2 attenuated but did not ameliorate PGI2 biosynthesis after PVL or prevent PHT. In contrast, treatment of COX-1−/− mice with NS398 or COX-2−/− mice with SC560 restricted PGI2 biosynthesis and abrogated the development of PHT following PVL. In conclusion, either COX-1 or COX-2 can mediate elevated PGI2 biosynthesis and the development of experimental prehepatic PHT. Consequently, PGI2 rather then COX-selective drugs are indicated in the treatment of PHT. Identification of additional target sites downstream of COX may benefit the >27,000 patients whom die annually from cirrhosis in the United States alone.

Role of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) derived prostaglandins (PG) in adaptive cytoprotection induced by mild stress

1998 ◽  
Vol 114 ◽  
pp. A82
Author(s):  
T. Brzozowski ◽  
P.C. Konturek ◽  
R. Pajdo ◽  
N. Nagraba ◽  
A. Szczeklik ◽  
...  
Keyword(s):  
Cyclooxygenase 2 ◽  
Mild Stress ◽  
Adaptive Cytoprotection ◽  
Cyclooxygenase 1 ◽  
Cox 2 ◽  
Cox 1

scholarly journals The role of brief intervention in achieving and maintaining abstinence in patients with alcoholic liver disease

2020 ◽  
pp. 182-188
Author(s):  
V. D. Lunkov ◽  
M. V. Maevskaya ◽  
V. T. Ivashkin
Keyword(s):  
Liver Disease ◽  
Alcoholic Liver Disease ◽  
Psychological Intervention ◽  
Decompensated Cirrhosis ◽  
Control Group ◽  
Factors Associated ◽  
Entire Observation Period ◽  
Group A ◽  
Observation Period

Objective of the study. prove the effectiveness of brief psychological intervention (BPI) conducted by an internist in achieving and maintaining abstinence in patients with alcoholic liver disease (ALD).Materials and methods. A total of 65 patients were included in the study: 29 patients in the BPI group and 36 in the historical control group. A comparative analysis of the frequency of achievement and maintenance of abstinence and analysis of factors associated with these parameters were conducted.Results of the study. The frequency of achieving abstinence was significantly higher in the BPI group compared with the control group after 6, 9, 12 and 24 months from the date of inclusion in the study (p <0.001, p = 0.002, p = 0.001, p = 0.017, respectively; criterion χ2). The frequency of failures to achieve abstinence in the CPC group was significantly lower than in the control group after 6 months and in general for the entire observation period (p = 0.004, p = 0.005, respectively; criterion χ2). Provision of BPIs for 12 months after alcohol-induced decompensation serves as a factor that is reliably associated with achieving total abstinence within 24 months (p = 0.001, criterion χ2). Decompensated cirrhosis of the liver serves as factors independently associated with failures to achieve abstinence within 24 months after alcohol-induced illness (OS: 10.72 [95% CI 2.17–52.81]; p = 0.004) and the absence of BPI after discharge from the hospital (OSH BPI: 0.80 [95% CI 0.14–0.479]; p = 0.006)Conclusion. BPIs provided by an internist to the patients with ABD for 12 months after alcohol-induced decompensation leads to a higher rate of achieving total abstinence and decrease in the frequency of failures to achieve abstinence within 24 months after discharge from the hospital.

scholarly journals The Role of Post-Ingestive Feedback in the Development of an Enhanced Appetite for the Orosensory Properties of Glucose over Fructose in Rats

Nutrients ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 807 ◽  
Author(s):  
Kevin P. Myers ◽  
Megan Y. Summers ◽  
Elizabeth Geyer-Roberts ◽  
Lindsey A. Schier
Keyword(s):  
Taste Receptor ◽  
Glucose Consumption ◽  
Sweet Taste ◽  
Taste Quality ◽  
Sensory Properties ◽  
Control Group ◽  
Sensory Property ◽  
Matched Group ◽  
Group A

The simple sugars glucose and fructose share a common “sweet” taste quality mediated by the T1R2+T1R3 taste receptor. However, when given the opportunity to consume each sugar, rats learn to affectively discriminate between glucose and fructose on the basis of cephalic chemosensory cues. It has been proposed that glucose has a unique sensory property that becomes more hedonically positive through learning about the relatively more rewarding post-ingestive effects that are associated with glucose as compared to fructose. We tested this theory using intragastric (IG) infusions to manipulate the post-ingestive consequences of glucose and fructose consumption. Food-deprived rats with IG catheters repeatedly consumed multiple concentrations of glucose and fructose in separate sessions. For rats in the “Matched” group, each sugar was accompanied by IG infusion of the same sugar. For the “Mismatched” group, glucose consumption was accompanied by IG fructose, and vice versa. This condition gave rats orosensory experience with each sugar but precluded the differential post-ingestive consequences. Following training, avidity for each sugar was assessed in brief access and licking microstructure tests. The Matched group displayed more positive evaluation of glucose relative to fructose than the Mismatched group. A second experiment used a different concentration range and compared responses of the Matched and Mismatched groups to a control group kept naïve to the orosensory properties of sugar. Consistent with results from the first experiment, the Matched group, but not the Mismatched or Control group, displayed elevated licking responses to glucose. These experiments yield additional evidence that glucose and fructose have discriminable sensory properties and directly demonstrate that their different post-ingestive effects are responsible for the experience-dependent changes in the motivation for glucose versus fructose.

scholarly journals Increased Interleukin-11 Levels Are Correlated with Cardiac Events in Patients with Chronic Heart Failure

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Jing Ye ◽  
Zhen Wang ◽  
Di Ye ◽  
Yuan Wang ◽  
Menglong Wang ◽  
...  
Keyword(s):  
Heart Failure ◽  
Plasma Concentrations ◽  
Heart Association ◽  
Functional Class ◽  
Control Group ◽  
Class Iii ◽  
Cardiac Events ◽  
Nyha Functional Class ◽  
Interleukin 11

Background. Interleukin-11 (IL-11) is an important inflammatory cytokine and has been demonstrated to participate in cardiovascular diseases. However, there have been no studies about the role of IL-11 in heart failure (HF). The present study is aimed at investigating whether IL-11 levels are associated with the cardiac prognosis in patients with HF. Methods. The plasma concentrations of IL-11 were measured in 240 patients with chronic HF (CHF) and 80 control subjects without signs of significant heart disease. In addition, we prospectively followed these CHF patients to endpoints of cardiac events. Results. Compared with the control group, the plasma IL-11 concentrations were significantly increased in the CHF patients and gradually increased in the New York Heart Association (NYHA) functional class II group, the NYHA functional class III group, and the NYHA functional class IV group. The receiver operating characteristic (ROC) curve revealed that the predictive role of IL-11 in HF is not as good as N-terminal B-type natriuretic peptide (BNP), although IL-11 has a certain value in predicting cardiac events. In addition, the CHF patients were divided into 3 groups according to the plasma IL-11 concentration category (low, T1; middle, T2; and high, T3). The multivariate Cox hazard analysis showed that the high plasma IL-11 concentrations were independently associated with the presence of cardiac events after adjustment for confounding factors. Furthermore, the CHF patients were divided into two groups based on the median plasma IL-11 concentrations. The Kaplan-Meier analysis revealed that the patients with high IL-11 concentrations had a higher risk of cardiac events compared with those with low IL-11 concentrations. Conclusions. Higher plasma IL-11 levels significantly increase the presence of cardiac events and suggest a poor outcome; although the diagnostic value of IL-11 in CHF is not as good as BNP, there is a certain value in predicting cardiac events in CHF.

scholarly journals Expression of COX-1, COX-2, 5-LOX and $$\hbox {CysLT}_2$$ in nasal polyps and bronchial tissue of patients with aspirin exacerbated airway disease

2019 ◽  
Vol 15 (1) ◽  
Author(s):  
Monique Vorsprach ◽  
Christoph Arens ◽  
Stephan Knipping ◽  
Dörte Jechorek ◽  
Sabine Stegemann-Koniszewski ◽  
...  
Keyword(s):  
Nasal Polyps ◽  
Sinus Surgery ◽  
Control Group ◽  
Bronchial Mucosa ◽  
Submucosal Glands ◽  
Patient Groups ◽  
Bronchial Tissue ◽  
Lower Airways ◽  
Cox 2 ◽  
Cox 1

Abstract Background Aspirin exacerbated respiratory disease (AERD) is a disease of the upper and lower airways. It is characterized by severe asthma, chronic sinusitis with nasal polyps (CRSwNP) and intolerance towards nonsteroidal analgesics (NSAR). Arachidonic acid (AA) metabolites play an important role in the pathogenesis of AERD. It is still unknown, whether metabolism of AA is comparable between the upper and lower airways as well as between patients with and without NSAR intolerance. Objective We sought to analyze differences in the expression of cyclooxygenases type 1 and 2 (COX-1, COX-2), arachidonate 5-lipoxygenase (5-LOX) and cysteinyl leukotriene receptor type 2 ($$\hbox {CysLT}_2$$CysLT2) in nasal polyps and the bronchial mucosa of patients with aspirin intolerant asthma (AIA, $$n=23$$n=23) as compared to patients with aspirin tolerant asthma (ATA, $$n=17$$n=17) and a control group with nasal polyps, but without asthma (NPwA, $$n=15$$n=15). Methods Tissue biopsies from nasal polyps and bronchial mucosa were obtained during surgical treatment of nasal polyps by endonasal functional endoscopic sinus surgery (FESS) under general anesthesia from intubated patients. Immunohistochemistry was used to analyze the expression of COX-1, COX-2, 5-LOX and $$\hbox {CysLT}_2$$CysLT2 in nasal and bronchial mucosa. Categorization into the different patient groups was performed according to the patient history, clinical and laboratory data, pulmonary function and provocation tests, as well as allergy testing. Results We observed a stronger expression of 5-LOX and $$\hbox {CysLT}_2$$CysLT2 in submucosal glands of nasal and bronchial tissue compared to epithelial expression. The expression of COX-1 and COX-2 was stronger in epithelia compared to submucosal glands. There was a similar expression of the enzymes and $$\hbox {CysLT}_2$$CysLT2 between upper and lower airways in all patient groups. We did not detect any significant differences between the patient groups. Conclusions The AA-metabolizing enzymes and the $$\hbox {CysLT}_2$$CysLT2 were expressed in a very similar way in different microscopic structures in samples of the upper and lower airways of individual patients. We did not detect differences between the patient groups indicating the pathogenetic role of AA metabolism in these disorders is independent of the presence of NSAR-intolerance.

Renal function in the laboratory rat: a student exercise.

1995 ◽  
Vol 268 (6) ◽  
pp. S49 ◽  
Author(s):  
R L Walker ◽  
M E Olson
Keyword(s):  
Renal Function ◽  
Fluid Intake ◽  
Tap Water ◽  
Extracellular Fluid ◽  
Control Group ◽  
Blood Samples ◽  
Treatment Groups ◽  
Laboratory Rats ◽  
Group A

Because of the increased concern over use of human body fluids in physiology teaching laboratories, we developed an exercise in renal function that utilizes laboratory rats. The purpose is to demonstrate the role of the kidneys in the homeostatic control of extracellular fluid volume, plasma ionic concentrations, and osmolarity. Three treatment groups are utilized: a volume-expanded (access to 1 g/100 ml sucrose) group, a volume-expanded and salt-loaded (access to 0.9 g/100 ml NaCl) group, and a volume-depleted (water-deprived) group. A normovolemic control group (access to tap water) is also included. Rats are housed individually in metabolic cages that allow accurate measurement of fluid intake and urine output. Blood samples are removed via cardiac puncture. The animals recover from this procedure and can be reutilized within 2-3 wk. When class data are pooled, clear trends are seen that demonstrate the volume-, osmo-, and ionoregulatory abilities of the kidneys.

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