RETRACTION: Role of Angiotensin-(1–7) in Gastroprotection against Stress-Induced Ulcerogenesis. The Involvement of Mas Receptor, Nitric Oxide, Prostaglandins, and Sensory Neuropeptides

Abstract

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, the agonist of Ang-(1-7) receptor, as well as the inhibition of nitricoxide (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)-1b, and tumor necrosis factor (TNF)-a 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-1b and TNF-a 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-1b and TNF-a 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-1b, and TNF-a.

Effect of vitamin K2 on the development of stress-induced osteopenia in a growing senescence-accelerated mouse prone 6 strain

“…WRS is often used as a stress treatment to induce stress response syndromes in animals (8)(9)(10)(11)(12)(13)24). In the present study, WRS successfully reduced the BMD via a high bone turnover rate; WRS induced an increase in bone resorption and formation.…”

“…VK2 has been shown to exhibit the novel function of binding to the pregnane X receptor (PXR), and PXR-dependent biological functions have been demonstrated in bone (6); however the biological effect of VK2 remains controversial, Effect of vitamin K2 on the development of stress-induced osteopenia in a growing senescence-accelerated mouse prone 6 strain since Fu et al (7) reported that VK2 failed to prevent bone loss in ovariectomized rats. Water-immersion restraint stress (WRS), which involves both psychological and physical stress, is widely used to induce reproducible stress ulcers in experimental animals (8)(9)(10)(11)(12). WRS consists of immobilization and cold stress, in which the exposure temperature is usually 24˚C.…”

Possible contribution of nitric oxide and prostaglandin in the protective effect of angiotensin (1-7) against stress induced gastric ulceration in adult male albino rats

“…In the present study, pre-treatment with Ang-(1-7) signifi cantly reduced the gastric ulcer index, gastric mucosal MDA level with concomitant increase in gastric mucosal concentrations of PGE 2 and NO in comparison with the CRS group. In addition, there was an improvement in the severe gastric damages that were observed by the histological examination.…”

“…The Angiotensin (1-7) is an important component of the RAS (2). Ang-(1-7) is a downstream peptide gen erated from angiotensin I through three known enzymes neprilysin (NEP), thimetoligopeptidase (TOP), and prolyloligopeptidase (POP)).…”

Brain neuropeptides in gastric mucosal protection

“…Such a phenomenon has been reported, for example, for amylin [21], adrenomedullin [19], TLQP-21 [16], or recently with angiotensin II [15,45] and substance P [10]. It might be speculated that some neuropeptides, especially in higher doses, are able to cross the brainblood barrier by non-saturable or saturable transport mechanisms using transporters (recently reviewed by Banks [46 ]) and enter the systemic circulation, where they may counteract the centrally induced gastroprotective action via peripheral mechanisms.…”