Ischemic preconditioning, the most effective gastroprotective intervention: involvement of prostaglandins, nitric oxide, adenosine and sensory nerves

Autor: Stanislaw J. Konturek, Peter C. Konturek, Slawomir Kwiecien, Eckhart G. Hahn, Danuta Drozdowicz, Zbigniew Sliwowski, Tomasz Brzozowski, Michal Pawlik, Robert Pajdo, Agata Ptak
Rok vydání: 2001
Předmět:
Male
Adenosine
Time Factors
medicine.medical_treatment
Indomethacin
Pharmacology
Nitroarginine
Lactones
chemistry.chemical_compound
Stilbenes
Sulfones
Enzyme Inhibitors
Ischemic Preconditioning
Reverse Transcriptase Polymerase Chain Reaction
Stomach
Denervation
cyclooxygenase
Isoenzymes
medicine.anatomical_structure
adenosine
Reperfusion Injury
Anesthesia
prostaglandin
CGRP (Calcitonin gene-related peptide)
Prostaglandin E
Sensory nerve
Calcitonin Gene-Related Peptide
Blotting
Western
Ischemia
Prostaglandin
gastric preconditioning
Nitric Oxide
Dinoprostone
Gene Expression Regulation
Enzymologic
Nitric oxide
Theophylline
medicine
Gastric mucosa
Animals
Cyclooxygenase Inhibitors
Neurons
Afferent
RNA
Messenger
Rats
Wistar
nitric oxide (NO)
Cyclooxygenase 2 Inhibitors
business.industry
adaptive cytoprotection
Receptors
Purinergic P1
Membrane Proteins
medicine.disease
ischemia/reperfusion
Peptide Fragments
Rats
Purinergic P1 Receptor Antagonists
chemistry
Cyclooxygenase 2
Gastric Mucosa
Prostaglandin-Endoperoxide Synthases
Regional Blood Flow
Resveratrol
Cyclooxygenase 1
Prostaglandins
Ischemic preconditioning
Capsaicin
Nitric Oxide Synthase
business
gastric blood flow
Digestive System
Zdroj: European Journal of Pharmacology. 427:263-276
ISSN: 0014-2999
DOI: 10.1016/s0014-2999(01)01246-8
Popis: Various organs, including heart, kidneys, liver or brain, respond to brief exposures to ischemia with an increased resistance to severe ischemia/reperfusion and this phenomenon is called "preconditioning". No study so far has been undertaken to check whether such short, repeated gastric ischemic episodes protect gastric mucosa against severe damage caused by subsequent prolonged ischemia/reperfusion and, if so, what could be the mechanism of this phenomenon. The ischemic preconditioning was induced by short episodes of gastric ischemia (occlusion of celiac artery from one to five times, for 5 min each) applied 30 min before prolonged (30 min) ischemia followed by 3 h of reperfusion or 30 min before topical application of strong mucosal irritants, such as 100% ethanol, 25% NaCl or 80 mM taurocholate. Exposure to regular 30-min ischemia, followed by 3-h reperfusion, produced numerous severe gastric lesions and significant fall in the gastric blood flow and prostaglandin E(2) generation. Short (5-min) ischemic episodes (1-5 times) by itself failed to cause any gastric lesions, but significantly attenuated those produced by ischemia/reperfusion. This protection was accompanied by a reversal of the fall in the gastric blood flow and prostaglandin E(2) generation and resembled that induced by classic gastric mild irritants. These protective and hyperemic effects of standard preconditioning were significantly attenuated by pretreatment with cyclooxygenase-2 and cyclooxygenase-1 inhibitors, such as indomethacin, Vioxx, resveratrol and nitric oxide (NO)-synthase inhibitor, N(G)-nitro-L-arginine (L-NNA). The protective and hyperemic effects of standard preconditioning were restored by addition of 16,16 dm prostaglandin E(2) or L-arginine, a substrate for NO synthase, respectively. Gastroprotective and hyperemic actions of standard ischemic preconditioning were abolished by pretreatment with capsaicin-inactivating sensory nerves, but restored by the administration of exogenous CGRP to capsaicin-treated animals. Gene and protein expression of cyclooxygenase-1, but not cyclooxygenase-2, were detected in intact gastric mucosa and in that exposed to ischemia/reperfusion with or without ischemic preconditioning, whereas cyclooxygenase-2 was overexpressed only in preconditioned mucosa. We conclude that: (1) gastric ischemic preconditioning represents one of the most powerful protective interventions against the mucosal damage induced by severe ischemia/reperfusion as well as by topical mucosal irritants in the stomach; (2) gastric ischemic preconditioning resembles the protective effect of "mild irritants" against the damage by necrotizing substances in the stomach acting via "adaptive cytoprotection" and involves several mediators, such as prostaglandin derived from cyclooxygenase-1 and cyclooxygenase-2, NO originating from NO synthase and sensory nerves that appear to play a key mechanism of gastric ischemic preconditioning.
Databáze: OpenAIRE
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