PT  - JOURNAL ARTICLE
AU  - Marcin Magierowski
AU  - Katarzyna Jasnos
AU  - Michal Pawlik
AU  - Gracjana Krzysiek-Maczka
AU  - Agata Ptak-Belowska
AU  - Rafal Olszanecki
AU  - Slawomir Kwiecien
AU  - Ryszard Korbut
AU  - Tomasz Brzozowski
TI  - RETRACTION: Role of Angiotensin-(1–7) in Gastroprotection against Stress-Induced Ulcerogenesis. The Involvement of Mas Receptor, Nitric Oxide, Prostaglandins, and Sensory Neuropeptides
AID  - 10.1124/jpet.113.207233
DP  - 2013 Dec 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 717--726
VI  - 347
IP  - 3
4099  - http://jpet.aspetjournals.org/content/347/3/717.short
4100  - http://jpet.aspetjournals.org/content/347/3/717.full
SO  - J Pharmacol Exp Ther2013 Dec 01; 347
AB  - Angiotensin-(1–7) [Ang-(1–7)] is a major vasoactive metabolite of angiotensin I (Ang I), both being important components of the renin-angiotensin system (RAS). Ang-(1–7) acting via Mas receptor was documented in kidneys, heart, brain, and gastrointestinal (GI)-tract. We studied the gastroprotective activity of exogenous Ang-(1–7) in rats exposed to water immersion and restraint stress (WRS) without or with A-779 [d-Ala7-Ang-(1–7), an antagonist of Ang-(1–7) Mas receptors], AVE 0991 (5-formyl-4-methoxy-2-phenyl-1[[4-[2-(ethylaminocarbonylsulfonamido)-5-isobutyl-3-thienyl]-phenyl]-methyl]-imidazole), the agonist of Ang-(1–7) receptor, as well as the inhibition of nitric-oxide (NO) synthase, the suppression of cyclo-oxygenase (COX)-1 (indomethacin, SC-560 [5-(4-chloro-phenyl)-1-(4-methoxyphenyl)-3-trifluoromethyl-pyrazole]), the activity COX-2 (rofecoxib), and denervation with capsaicin. The mRNA expression of constitutively expressed nitric-oxide synthase (cNOS), inducible nitric-oxide synthase (iNOS), interleukin (IL)-1β, and tumor necrosis factor (TNF)-α was analyzed by reverse transcription polymerase chain reaction. The WRS lesions were dose-dependently reduced by pretreatment with Ang-(1–7), which also caused an increase in gastric blood flow (GBF) and luminal content of NO. COX-1 and COX-2 inhibitors or L-NNA (N5-[imino(nitroamino)methyl]-L-ornithine) reversed the reduction in lesion number and the rise in GBF evoked by Ang-(1–7). Ang II augmented the WRS lesions, decreased GBF and increased the plasma IL-1β and TNF-α levels. Capsaicin denervation attenuated the reduction of Ang-(1–7)-induced gastric lesions and the rise in GBF; these effects were restored by supplementation with calcitonin gene–related peptide (CGRP). The cNOS mRNA was upregulated while iNOS, IL-1β and TNF-α mRNAs were downregulated in Ang-(1–7)-pretreated rats. We conclude that Ang-(1–7), in contrast to Ang II, which worsened WRS ulcerogenesis, affords potent gastroprotection against WRS ulcerogenesis via an increase in GBF mediated by NO, endogenous prostaglandins, sensory neuropeptides, and anti-inflammatory action involving the inhibition of proinflammatory markers iNOS, IL-1β, and TNF-α.