title: Exogenous asymmetric dimethylarginine (ADMA) in pathogenesis of ischemia-reperfusion-induced gastric lesions: interaction with protective nitric oxide (NO) and calcitonin gene-related peptide (CGRP).
abstract: Asymmetric dimethylarginine (ADMA) is an endogenous nitric oxide (NO) synthesis inhibitor and pro-inflammatory factor. We investigated the role of ADMA in rat gastric mucosa compromised through 30 min of gastric ischemia (I) and 3 h of reperfusion (R). These I/R animals were pretreated with ADMA with or without the combination of L-arginine, calcitonin gene-related peptide (CGRP) or a small dose of capsaicin, all of which are known to afford protection against gastric lesions, or with a farnesoid X receptor (FXR) agonist, GW 4064, to increase the metabolism of ADMA. In the second series, ADMA was administered to capsaicin-denervated rats. The area of gastric damage was measured with planimetry, gastric blood flow (GBF) was determined by H2-gas clearance, and plasma ADMA and CGRP levels were determined using ELISA and RIA. ADMA significantly increased I/R-induced gastric injury while significantly decreasing GBF, the luminal NO content, and the plasma level of CGRP. This effect of ADMA was significantly attenuated by pretreatment with CGRP, L-arginine, capsaicin, or a PGE2 analogue. In GW4064 pretreated animals, the I/R injury was significantly reduced and this effect was abolished by co-treatment with ADMA. I/R damage potentiated by ADMA was exacerbated in capsaicin-denervated animals with a further reduction of CGRP. Plasma levels of IL-10 were significantly decreased while malonylodialdehyde (MDA) and plasma TNF-α contents were significantly increased by ADMA. In conclusion, ADMA aggravates I/R-induced gastric lesions due to a decrease of GBF, which is mediated by a fall in NO and CGRP release, and the enhancement of lipid peroxidation and its pro-inflammatory properties.
authors.affiliation: Department of Physiology, Jagiellonian University Medical College, Grzegorzecka Street 16, Cracow 31-531, Poland. m.magierowski@uj.edu.pl.
authors.forename: Marcin
authors.initials: M
authors.lastname: Magierowski
authors.affiliation: Department of Physiology, Jagiellonian University Medical College, Grzegorzecka Street 16, Cracow 31-531, Poland. k.jasnos@interia.pl.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Jasnos
authors.affiliation: Department of Physiology, Jagiellonian University Medical College, Grzegorzecka Street 16, Cracow 31-531, Poland. agazs@poczta.fm.
authors.forename: Zbigniew
authors.initials: Z
authors.lastname: Sliwowski
authors.affiliation: Department of Physiology, Jagiellonian University Medical College, Grzegorzecka Street 16, Cracow 31-531, Poland. marcin.surmiak@uj.edu.pl.
authors.forename: Marcin
authors.initials: M
authors.lastname: Surmiak
authors.affiliation: Department of Physiology, Jagiellonian University Medical College, Grzegorzecka Street 16, Cracow 31-531, Poland.
authors.forename: Gracjana
authors.initials: G
authors.lastname: Krzysiek-Maczka
authors.affiliation: Department of Physiology, Jagiellonian University Medical College, Grzegorzecka Street 16, Cracow 31-531, Poland.
authors.forename: Agata
authors.initials: A
authors.lastname: Ptak-Belowska
authors.affiliation: Department of Physiology, Jagiellonian University Medical College, Grzegorzecka Street 16, Cracow 31-531, Poland. skwiecien@cm-uj.krakow.pl.
authors.forename: Slawomir
authors.initials: S
authors.lastname: Kwiecien
authors.affiliation: Department of Physiology, Jagiellonian University Medical College, Grzegorzecka Street 16, Cracow 31-531, Poland. mpbrzozo@cyf-kr.edu.pl.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Brzozowski
mesh_terms: D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology; D001783:Blood Flow Velocity / Q000187:drug effects; D015740:Calcitonin Gene-Related Peptide / Q000097:blood / Q000494:pharmacology*; D002211:Capsaicin / Q000494:pharmacology; D004347:Drug Interactions; D004797:Enzyme-Linked Immunosorbent Assay; D005753:Gastric Mucosa / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism; D016753:Interleukin-10 / Q000097:blood; D007555:Isoxazoles / Q000494:pharmacology; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D009569:Nitric Oxide / Q000378:metabolism*; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000150:complications*; D013272:Stomach Diseases / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D007555:Isoxazoles; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D009569:Nitric Oxide; D008315:Malondialdehyde; C018524:N,N-dimethylarginine; D001120:Arginine; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin; C412815:GW 4064