Int. J. Mol. Sci. 2014, 15(3), 4946-4964; doi:10.3390/ijms15034946
Article

Exogenous Asymmetric Dimethylarginine (ADMA) in Pathogenesis of Ischemia-Reperfusion-Induced Gastric Lesions: Interaction with Protective Nitric Oxide (NO) and Calcitonin Gene-Related Peptide (CGRP)

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Received: 27 December 2013; in revised form: 3 March 2014 / Accepted: 4 March 2014 / Published: 20 March 2014
(This article belongs to the Special Issue ADMA and Nitrergic System)
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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.
Keywords: asymmetric dimethyl arginine; gastric mucosa; ischemia/reperfusion; farnesoid X receptor; gastric damage; sensory neurons; calcitonin gene-related peptide; capsaicin
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Magierowski, M.; Jasnos, K.; Sliwowski, Z.; Surmiak, M.; Krzysiek-Maczka, G.; Ptak-Belowska, A.; Kwiecien, S.; Brzozowski, T. Exogenous Asymmetric Dimethylarginine (ADMA) in Pathogenesis of Ischemia-Reperfusion-Induced Gastric Lesions: Interaction with Protective Nitric Oxide (NO) and Calcitonin Gene-Related Peptide (CGRP). Int. J. Mol. Sci. 2014, 15, 4946-4964.

AMA Style

Magierowski M, Jasnos K, Sliwowski Z, Surmiak M, Krzysiek-Maczka G, Ptak-Belowska A, Kwiecien S, Brzozowski T. Exogenous Asymmetric Dimethylarginine (ADMA) in Pathogenesis of Ischemia-Reperfusion-Induced Gastric Lesions: Interaction with Protective Nitric Oxide (NO) and Calcitonin Gene-Related Peptide (CGRP). International Journal of Molecular Sciences. 2014; 15(3):4946-4964.

Chicago/Turabian Style

Magierowski, Marcin; Jasnos, Katarzyna; Sliwowski, Zbigniew; Surmiak, Marcin; Krzysiek-Maczka, Gracjana; Ptak-Belowska, Agata; Kwiecien, Slawomir; Brzozowski, Tomasz. 2014. "Exogenous Asymmetric Dimethylarginine (ADMA) in Pathogenesis of Ischemia-Reperfusion-Induced Gastric Lesions: Interaction with Protective Nitric Oxide (NO) and Calcitonin Gene-Related Peptide (CGRP)." Int. J. Mol. Sci. 15, no. 3: 4946-4964.


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