title: Ischemic preconditioning of remote organs attenuates gastric ischemia-reperfusion injury through involvement of prostaglandins and sensory nerves.
abstract: Limitation of the stomach damage by its earlier brief ischemia and reperfusion before prolonged ischemia is defined as gastric ischemic preconditioning but whether such brief ischemia of remote organs like heart or liver can also attenuate the gastric damage caused by longer and severe ischemia-reperfusion remains unknown. The cardiac, hepatic and gastric preconditioning were induced by brief ischemia (occlusion of coronary, hepatic and celiac arteries twice for 5 min) applied 30 min before 3 h of ischemia/reperfusion. Standard 3 h ischemia-reperfusion of the stomach produced numerous gastric lesions, decreased gastric blood flow and mucosal prostaglandin E2 generation and increased expression and plasma release of interleukin-1beta and tumor necrosis factor-alpha (TNF-alpha). These effects were significantly attenuated by brief cardiac, hepatic and gastric preconditioning which upregulated cyclooxygenase-2 mRNA but not cyclooxygenase-1 mRNA. The protective effects of brief gastric, cardiac and hepatic preconditioning were attenuated by selective cyclooxygenase-1 and cyclooxygenase-2 inhibitors and capsaicin denervation. We conclude that brief ischemia of remote preconditioning such as heart or liver protects gastric mucosa against severe ischemia-reperfusion-induced gastric lesions as effectively as local preconditioning of the stomach itself via the mechanism involving prostaglandin derived from cyclooxygenase-1 and cyclooxygenase-2 and the activation of sensory nerves releasing calcitonin gene-related peptide (CGRP) combined with the suppression of interleukin-1beta and TNF-alpha expression and release.
authors.affiliation: Department of Physiology, Jagiellonian University Medical College, 16, Grzegorzecka Str., 31-531 Cracow, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Brzozowski
authors.forename: Peter C
authors.initials: PC
authors.lastname: Konturek
authors.forename: Stanislaw J
authors.initials: SJ
authors.lastname: Konturek
authors.forename: Robert
authors.initials: R
authors.lastname: Pajdo
authors.forename: Slawomir
authors.initials: S
authors.lastname: Kwiecien
authors.forename: Michal
authors.initials: M
authors.lastname: Pawlik
authors.forename: Danuta
authors.initials: D
authors.lastname: Drozdowicz
authors.forename: Zbigniew
authors.initials: Z
authors.lastname: Sliwowski
authors.forename: Wieslaw W
authors.initials: WW
authors.lastname: Pawlik
mesh_terms: D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism / Q000494:pharmacology; D002211:Capsaicin / Q000494:pharmacology; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D003714:Denervation; D015232:Dinoprostone / Q000378:metabolism; D005753:Gastric Mucosa / Q000098:blood supply / Q000294:innervation / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D007213:Indomethacin / Q000494:pharmacology; D007375:Interleukin-1 / Q000097:blood; D019194:Ischemic Preconditioning; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000235:genetics; D007783:Lactones / Q000494:pharmacology; D008297:Male; D008565:Membrane Proteins; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics; D011453:Prostaglandins / Q000378:metabolism*; D011720:Pyrazoles / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000503:physiopathology* / Q000517:prevention & control; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013270:Stomach / Q000098:blood supply / Q000473:pathology; D013450:Sulfones / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007375:Interleukin-1; D007527:Isoenzymes; D007783:Lactones; D008565:Membrane Proteins; D011453:Prostaglandins; D011720:Pyrazoles; D012333:RNA, Messenger; C115461:SC 560; D013450:Sulfones; D014409:Tumor Necrosis Factor-alpha; C116926:rofecoxib; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C496513:Ptgs1 protein, rat; D015740:Calcitonin Gene-Related Peptide; D015232:Dinoprostone; D002211:Capsaicin; D007213:Indomethacin