Expressions of Inducible Nitric Oxide Synthase and Cyclooxygenase-2 in Gastric Ischemia-Reperfusion: Role of Angiotensin II

Gemici, Burcu; Tan, Ruken; Öngüt, Gözde; İzgüt‐Uysal, V. Nimet

doi:10.1016/j.jss.2009.07.018

Cited by 22 publications

(13 citation statements)

References 46 publications

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“…These results lend further support to prior studies that demonstrated protective effects of ARBs including candesartan [14], losartan, [39], olmesartan [40] and telmisartan [41]. Prior evidence demonstrated the protective effects of ARBs via reducing iNOS expression in various models [42-44]. To our knowledge, this is the first report that links the vascular protective effect of candesartan to modulating iNOS expression in the ischemic retinopathy model.…”

Section: Discussionsupporting

confidence: 87%

Candesartan stimulates reparative angiogenesis in ischemic retinopathy model: role of hemeoxygenase-1 (HO-1)

et al. 2014

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Ischemic diseases such as stroke and proliferative retinopathy are characterized by hypoxia-driven release of angiogenic factors such as vascular endothelial growth factor (VEGF). However, revascularization of the ischemic areas is inadequate resulting in impaired neuro-vascular function. We aim to examine the vascular protective effects of candesartan, an angiotensin receptor blocker, in an ischemic retinopathy mouse model. Vascular density, number of tip cells, and perfusions of capillaries were assessed. Activation of Muller glial cells and levels of peroxynitrite, VEGF, VEGFR2, inducible- nitric oxide synthase, hemoxygenase-1 (HO-1) were assessed. Proangiogenic effects of candesartan were examined in human endothelial cells (EC) that were cultured in normoxia or hypoxia and transduced with siRNA against HO-1. Candesartan (1mg/kg) and (10mg/kg) decreased hypoxia-induced neovascularization by 67% and 70%, respectively. Candesartan (10mg/kg) significantly stimulated the number of tip cells and physiological revascularization of the central retina (45%) compared to untreated pups. The effects of candesartan coincided with reduction of hypoxia-induced Muller glial activation, iNOS expression and restoration of HO-1 expression with no significant change in VEGF levels. In vitro, silencing HO-1 expression blunted the ability of candesartan to induce VEGF expression under normoxia and VEGFR2 activation and angiogenic response under both normoxia and hypoxia. These findings suggest that candesartan improved reparative angiogenesis and hence prevented pathological angiogenesis by modulating HO-1 and iNOS levels in ischemic retinopathy. HO-1 is required for VEGFR2 activation and proangiogenic action of candesartan in EC. Candesartan, an FDA-approved drug could be repurposed as a potential therapeutic agent for the treatment of ischemic diseases.

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Section: Discussionsupporting

confidence: 87%

Candesartan stimulates reparative angiogenesis in ischemic retinopathy model: role of hemeoxygenase-1 (HO-1)

et al. 2014

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“…Ang II receptor subtypes AT 1 and AT 2 were detected in the human esophageal, gastric, small intestinal, and colonic mucosa (Hirasawa et al, 2002;Casselbrant et al, 2009;Hallersund et al, 2011). The antagonists of Ang II AT 1 receptors attenuated gastric injury induced by ischemia-reperfusion, cold stress, and indomethacininduced damage in rodents due to an inhibition of sympathoadrenal axis and the attenuation of vasoconstrictor and proinflammatory activity of Ang II (Pavel et al, 2008;Morsy et al, 2009;Gemici et al, 2010;Saavedra et al, 2011;Shiotani et al, 2011).…”

Section: Abbreviationsmentioning

confidence: 99%

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

Magierowski

Jasnos

Pawlik

et al. 2013

J Pharmacol Exp Ther

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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.

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“…Prostaglandin E2 levels were determined by the method described previously (Gemici et al 2010;Carlton et al 2002). Whole SN and retina tissues were homogenized in 0.25 ml Tris-HCl buffer (pH: 7.5) with 0.02 M EDTA and 5 mg/ml of indomethacin.…”

Section: Determination Of Prostaglandin E2 Tissue Contentmentioning

confidence: 99%

The Effect of Docosahexaenoic Acid on Visual Evoked Potentials in a Mouse Model of Parkinson’s Disease: The Role of Cyclooxygenase-2 and Nuclear Factor Kappa-B

et al. 2011

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This study aimed to investigate the effect of docosahexaenoic acid (DHA) on visual evoked potentials (VEPs) in a mice model of Parkinson's disease (PD). Mice model was created by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and DHA was given by gavage. Cyclooxygenase-2 (COX-2), caspase-3 activities, nuclear factor kappa-B (NF-κB) and prostaglandin E2 (PGE2) levels were determined in substantia nigra (SN) and retina. Cyclooxygenase-2 intensities were also determined immunohistochemically. The tyrosine hydroxylase (TH) immunolabelling was significantly decreased in MPTP group compared to control. Docosahexaenoic acid decreased dopaminergic neuron death in MPTP + DHA group when compared to MPTP group. Mice treated with MPTP showed motor deficits as compared to control. Significant improvement was observed in MPTP + DHA group when compared to MPTP group. Treatment with MPTP significantly increased the activity of COX-2 and total COX in SN when compared to the control group. Docosahexaenoic acid caused a significant decrease in total COX and COX-2 activity in SN of mice given MPTP. Cyclooxygenase-2 showed strong immunostaining in MPTP group when compared to other groups in SN. Levels of PGE2 increased in MPTP group when compared to control in SN. Docosahexaenoic acid treatment in MPTP group reduced PGE2 in SN. Nuclear factor kappa-B levels were found to be decreased in SN of MPTP group. The mean latencies of P1, N1, P2, N2, P3, N3, P4, N4, and P5 VEP components were significantly prolonged in MPTP group when compared to control. In MPTP + DHA group, the mean latencies of all components except P5 returned to control values. Current data shows that DHA treatment improves prolonged VEPs latencies and locomotor activity.

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Expressions of Inducible Nitric Oxide Synthase and Cyclooxygenase-2 in Gastric Ischemia-Reperfusion: Role of Angiotensin II

Cited by 22 publications

References 46 publications

Candesartan stimulates reparative angiogenesis in ischemic retinopathy model: role of hemeoxygenase-1 (HO-1)

Candesartan stimulates reparative angiogenesis in ischemic retinopathy model: role of hemeoxygenase-1 (HO-1)

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

The Effect of Docosahexaenoic Acid on Visual Evoked Potentials in a Mouse Model of Parkinson’s Disease: The Role of Cyclooxygenase-2 and Nuclear Factor Kappa-B

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