thromboxane-a2 and Peptic-Ulcer

Topics: Anti-Inflammatory Agents, Non-Steroidal; Anticarcinogenic Agents; Aspirin; Blood Platelets; Cardiovascular Diseases; Celecoxib; Colorectal Neoplasms; Cyclooxygenase 1; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Depression, Chemical; Dinoprostone; Epoprostenol; Gastric Mucosa; Gastrointestinal Hemorrhage; Humans; Incidence; Intestinal Mucosa; Isoenzymes; Lactones; Membrane Proteins; Peptic Ulcer; Prostaglandin-Endoperoxide Synthases; Prostaglandins; Pyrazoles; Randomized Controlled Trials as Topic; Substrate Specificity; Sulfonamides; Sulfones; Thromboembolism; Thromboxane A2; Treatment Outcome

Chronic non-specific pulmonary diseases are frequently followed by the development of inflammatory-degenerative and erosive-ulcerative processes in the mucous membrane of the stomach and duodenum. The literature date are presented on the frequency of combination of these conditions, the attempt is made to assess their link from the viewpoint of pathogenesis. Disturbances of respiratory lung function and hypoxia as well as non-respiratory metabolic functions of the pulmonary tissue are regarded as etiological factors of pathological processes in the gastro-duodenal area.

Topics: Adult; Angiotensins; Arachidonic Acid; Arachidonic Acids; Chronic Disease; Duodenal Diseases; Duodenitis; Female; Gastritis; Histamine; Humans; Hypoxia; Leukotriene B4; Lung; Lung Diseases; Male; Middle Aged; Peptic Ulcer; Prostaglandins; SRS-A; Stomach Diseases; Thromboxane A2

Topics: Animals; Anti-Inflammatory Agents; Arachidonic Acids; Epoprostenol; Gastric Juice; Gastric Mucosa; Peptic Ulcer; Prostaglandin Antagonists; Prostaglandins; Rabbits; Rats; Regional Blood Flow; Thromboxane A2

We studied whether administration of nitroflurbiprofen (HCT-1026), a cyclooxygenase inhibitor with nitric oxide (NO)-donating properties, modulates the increased intrahepatic vascular tone in portal hypertensive cirrhotic rats.. In vivo hemodynamic measurements (n = 8/condition) and evaluation of the increased intrahepatic resistance by in situ perfusion (n = 5/condition) were performed in rats with thioacetamide-induced cirrhosis that received either nitroflurbiprofen (45 mg/kg), flurbiprofen (30 mg/kg, equimolar concentration to nitroflurbiprofen), or vehicle by intraperitoneal injection 24 hours and 1 hour prior to the measurements. Additionally, we evaluated the effect of acute administration of both drugs (250 micromol/L) on the intrahepatic vascular tone in the in situ perfused cirrhotic rat liver (endothelial dysfunction and hyperresponsiveness to methoxamine) and on hepatic stellate cell contraction in vitro. Typical systemic adverse effects of nonsteroidal anti-inflammatory drugs, such as gastrointestinal ulceration, renal insufficiency, and hepatotoxicity, were actively explored.. In vivo, nitroflurbiprofen and flurbiprofen equally decreased portal pressure (8 +/- 0.8 and 8.4 +/- 0.1 mm Hg, respectively, vs 11.8 +/- 0.6 mm Hg) and reduced the total intrahepatic vascular resistance. Systemic hypotension was not aggravated in the different treatment groups (P = .291). In the perfused cirrhotic liver, both drugs improved endothelial dysfunction and hyperresponsiveness. This was associated with a decreased hepatic thromboxane A(2)-production and an increased intrahepatic nitrate/nitrite level. In vitro, nitroflurbiprofen, more than flurbiprofen, decreased hepatic stellate cells contraction. Flurbiprofen-treated rats showed severe gastrointestinal ulcerations (bleeding in 3/8 rats) and nefrotoxicity, which was not observed in nitroflurbiprofen-treated cirrhotic rats.. Treatment with nitroflurbiprofen, an NO-releasing cyclooxygenase inhibitor, improves portal hypertension without major adverse effects in thioacetamide-induced cirrhotic rats by attenuating intrahepatic vascular resistance, endothelial dysfunction, and hepatic hyperreactivity to vasoconstrictors.

Topics: Animals; Cyclooxygenase Inhibitors; Disease Models, Animal; Dose-Response Relationship, Drug; Endothelium, Vascular; Flurbiprofen; Hypertension, Portal; Kidney Diseases; Liver; Liver Circulation; Liver Cirrhosis, Experimental; Male; Nitric Oxide; Nitric Oxide Donors; Peptic Ulcer; Perfusion; Portal Pressure; Rats; Rats, Wistar; Thioacetamide; Thromboxane A2; Vascular Resistance; Vasoconstriction; Vasodilation

Topics: Diarrhea; Gastric Mucosa; Gastrointestinal Diseases; Gastrointestinal Motility; Humans; Intestinal Mucosa; Leukotriene B4; Lipoxygenase; Peptic Ulcer; Prostaglandin-Endoperoxide Synthases; Prostaglandins; Prostaglandins E, Synthetic; SRS-A; Thromboxane A2