Gastric Ischemia-reperfusion Injury Research Articles

The effects of sugammadex on gastric ischemia-reperfusion injury in rats: Biochemical and histopathological evaluation.

The primary sources of reactive oxygen species (ROS) that cause ischemia-reperfusion (I/R) injuries are enzymes xanthine oxidase (XO) and nicotinamide adenine dinucleotide phosphate oxidases (NOXs) in the literature, whereby one of the main ROS producing cells via NOX activity are polymophonuclear leukocytes (PNL). Sugammadex, the effect of which we plan to research against gastric I/R damage, is a modified gamma-cyclodextrin that antagonizes the action of steroidal neuromuscular blocking drugs. Previous studies have reported that sugammadex inhibits PNL infiltration. However, it is unknown whether an inhibitory effect on XO is present. We aimed to biochemically and histopathologically investigate the effects of sugammadex on I/R-induced stomach damage in rats. The animals were divided into groups that underwent gastric ischemia-reperfusion (GIR), 4 mg/kg sugammadex + gastric ischemia-reperfusion (SGIR), and a sham operation group (SG). The effect of sugammadex was evaluated by measuring oxidant-antioxidant and PNL parameters. There was no significant difference in XO levels between the SGIR and GIR groups. In the SGIR group, sugammadex inhibited the increase in myeloperoxidase (MPO) and malondialdehyde (MDA) levels (p < 0.001). The amount of MDA and MPO in the SGIR group was similar as in the SG group. Sugammadex significantly suppressed the decrease in tGSH levels in the SGIR group (p < 0.001). The difference between tGSH levels in the SG and SGIR groups was slight. In the SGIR group, sugammadex significantly suppressed the increase in tumor necrosis factor alpha (TNF-α) and interleukin 1 beta (IL1-β) levels compared to the GIR group (p < 0.001). Additionally, sugammadex corrected histopathological modifications as much as sham group. In conclusion, sugammadex may be beneficial in preventing oxidative stress.

Autophagy-lysosome dysfunction is involved in gastric ischemia-reperfusion injury by promoting microglial activation in the paraventricular nucleus.

The hypothalamic paraventricular nucleus (PVN) is a specific center in the brain that regulates gastric mucosal injury following gastric ischemia-reperfusion (GI-R) injury. This study aimed to investigate whether autophagy-lysosome dysfunction in the PVN tissues of GI-R rats is involved in the gastric injury, and the underlying molecular mechanisms. The rat model of GI-R was established by clamping the celiac artery for 30 min and reperfusion for different hours (1, 3, and 6 h). The gastric injury was evaluated by hematoxylin and eosin staining of the stomachand the gastric mucosal index. The autophagy-lysosome dysfunction in the PVN was evaluated by the protein levels of LC3 II and Beclin-1 (markers for autophagosome activity) and the activity of acid phosphatase (a representative lysosomal enzyme). Immunohistochemical staining of ionized calcium-binding adaptor molecule 1 in the PVN was performed to evaluate microglial activation. Reactive oxygen species (ROS) content and phosphorylated γ-aminobutyric acid B receptor (p-GABAB R) expression in the PVN were also examined. The results revealed that, in GI-R rats, the shorter the reperfusion duration, the more severe the gastric mucosal damage. The autophagy-lysosome dysfunction exhibited by GI-R rats further enhanced microglial activation, ROS production, p-GABAB R expression, and gastric injury. In addition, activating microglial cells increased ROS production, p-GABAB R expression, and gastric injury in GI-R rats,while inhibiting microglial activation resulted in the opposite results. Taken together, autophagy-lysosome dysfunction induced by GI-R aggravated the gastric injury by inducing microglia activation.

Liraglutide protects against lethal renal ischemia-reperfusion injury by inhibiting high-mobility group box 1 nuclear-cytoplasmic translocation and release

Liraglutide, a glucagon-like peptide-1 receptor (GLP-1R) agonist, has been reported to exert protective effects against myocardial, hepatic, and gastric ischemia-reperfusion injury (IRI), but whether it can protect against renal IRI remains unknown. Here, a lethal renal IRI model was established with a 100% mortality rate in untreated mice. Treatment with liraglutide involving a regimen of multiple doses resulted in 100% survival, remarkable preservation of renal function, a significant reduction in pathological damage, and blunted upregulation of TNF-α, IL-1β, IL-6, MCP-1, TLR-2, TLR-4, and RAGE mRNA. We found that liraglutide treatment dramatically inhibited ischemia-induced nucleocytoplasmic translocation and release of HMGB1. This inhibition was associated with a marked decrease (~ 60%) in nuclear histone acetyltransferase activity. In addition, the protective effects of liraglutide on renal IRI were largely abolished by the administration of exogenous HMGB1. When the GLP-1R antagonist exendin (9-39) was given to mice before each liraglutide administration, or GLP-1R-/- mice were used for the renal IRI experiments, the protective effect of liraglutide on renal IRI was partially reversed. Moreover, liraglutide pretreatment significantly inhibited HMGB1 nucleocytoplasmic translocation during hypoxic culture of HK-2 cells in vitro, but the addition of exendin (9-39) significantly eliminated this inhibition. We demonstrate here that liraglutide can exert a strong protective effect on lethal renal IRI in mice. This protection appears to be related to the inhibition of HMGB1 nuclear-cytoplasmic translocation and release and partially depends on GLP-1R. Thus, liraglutide may be therapeutically useful for the clinical prevention and treatment of organ IRI.

The effect of dexmedetomidine on gastric ischemia reperfusion injury in rats. Biochemical and histopathological evaluation.

ABSTRACTPurpose:To evaluate the protective effect of dexmedetomidine on gastric injury induced by ischemia reperfusion (I/R) in rats.Methods:A total of 18 male albino Wistar rats were divided groups as: gastric ischemia reperfusion (GIR), gastric ischemia reperfusion and 50 μg/kg dexmedetomidine (DGIR) and sham operation (HG) group. After the third hour of reperfusion, the biochemical and histopathological examinations were performed on the removed stomach tissue.Results:Malondialdehyde (MDA) and myeloperoxidase (MPO) levels were found to be significantly higher in GIR compared to HG (p < 0.05). A statistically significant decrease was observed at the DGIR compared to the GIR for oxidants levels. Total glutathione (tGSH) and superoxide dismutase (SOD) levels were statistically significantly decreased at the GIR, and antioxidants levels were found to be significantly higher in the DGIR (p < 0.05) There was no significant difference between HG and DGIR in terms of SOD (p = 0.097). The DGIRs’ epitheliums, glands and vascular structures were close to normal histological formation.Conclusions:Dexmedetomidine is found to prevent oxidative damage on the stomach by increasing the antioxidant effect. These results indicate that dexmedetomidine may be useful in the treatment of ischemia-reperfusion-related gastric damage.

Alpha-lipoic acid and its protective impact against gastric ischemiareperfusion injury in rats

Alpha-lipoic acid and its protective impact against gastric ischemiareperfusion injury in rats

Positive acceleration adaptive training attenuates gastric ischemia-reperfusion injury through COX-2 and PGE2 expression.

The mechanism involved in the effects of positive acceleration adaptive training (PAAT) on gastric ischemia-reperfusion injury (GI-RI) has not been fully characterized. The aim of the present study was to investigate the effects of PAAT in attenuating GI-RI in a rat model. The inflammatory factor and caspase-3 levels were measured using ELISA kits. A western blot assay was used to analyze tumor necrosis factor-α (TNF)-α, tumor necrosis factor receptor 1 (TNFR1), tumor necrosis factor-related apoptosis inducing ligand (TRAIL), death receptor (DR) 4, DR5, cyclooxygenase (COX)-2, COX-1 and prostaglandin E2 (PGE2) protein expression levels. It was revealed that PAAT could alleviate GI-RI and inflammatory factor levels in a rat model. PAAT suppressed TNF-α and TNFR1 protein expression levels, inhibited TRAIL, DR4, DR5, COX-2 and PGE2 protein expression levels; however, it did not have an effect on COX-1 protein expression in the model of GI-RI. The data indicated that the effects of PAAT attenuated GI-RI through the downregulation of COX-2 and PGE2 expression.

Effect of H2S on gastric ischemia-reperfusion injury in rats

Effect of H₂S on gastric ischemia-reperfusion injury in rats

The Regulatory Effects of Lateral Hypothalamus Area GABAB Receptor on Gastric Ischemia-Reperfusion Injury in Rats.

HIGHLIGHTS The aim of the research was to determine the functional effects and molecular mechanisms of GABAB receptor on ischemia reperfusion-induced gastric injury in rats.The lateral hypothalamus area GABAB receptor attenuated the ischemia reperfusion-induced gastric injury by up-regulating the production of GABA, GABABR, and down-regulating P-GABABR in the brain.This work would provide a new therapeutic strategy for acute gastric injury.Gastric ischemia-reperfusion (GI-R) injury progression is largely associated with excessive activation of the greater splanchnic nerve (GSN). This study aims to investigate the protective effects of GABAB receptor (GABABR) in the lateral hypothalamic area (LHA) on GI-R injury. A model of GI-R injury was established by clamping the celiac artery for 30 min and then reperfusion for 1 h. The coordinate of FN and LHA was identified in Stereotaxic Coordinates and then the L-Glu was microinjected into FN, GABAB receptor agonist baclofen, or GABAB receptor antagonist CGP35348 was microinjected into the LHA, finally the GI-R model was prepared. The expression of GABABR, P-GABABR, NOX2, NOX4, and SOD in the LHA was detected by western blot, PCR, and RT-PCR. The expression of IL-1β, NOX2, and NXO4 in gastric mucosa was detected by western blot. We found that microinjection of L-Glu into the FN or GABAB receptor agonist (baclofen) into the LHA attenuated GI-R injury. Pretreatment with GABAB receptor antagonist CGP35348 reversed the protective effects of FN stimulation or baclofen into the LHA. Microinjection of baclofen into the LHA obviously reduced the expression of inflammatory factor IL-1β, NOX2, and NOX4 in the gastric mucosa.Conclusion: The protective effects of microinjection of GABABR agonist into LHA on GI-R injury in rats could be mediated by up-regulating the production of GABA, GABABR, and down-regulating P-GABABR in the LHA.

A preliminary study of the anti-inflammatory and anti-apoptotic effects of crocin against gastric ischemia-reperfusion injury in rats

The aim of the present study was to investigate the protective effect of crocin on gastric mucosal lesions caused by ischemia-reperfusion (I/R) injury in rats. Thirty-two male rats were randomly divided into sham, I/R, I/R + crocin pretreatment and crocin alone groups. To induce I/R lesions, the celiac artery was clamped for 30 min, and the clamp was then removed to allow reperfusion for 3 h. Crocin-pretreated rats received crocin (15 mg/kg, i.p.) 30 min prior to the induction of I/R injury. Samples of gastric mucosa were collected to quantify the protein expression of caspase-3, an apoptotic factor, and inducible nitric oxide synthase (iNOS), a pro-inflammatory protein, by Western blot. Pretreatment with crocin decreased the total area of gastric lesions and decreased the protein expression levels of caspase-3 and iNOS induced by I/R injury. Our findings showed a protective effect of crocin in gastric mucosa against I/R injury. This effect of crocin was mainly mediated by reducing the protein expression of iNOS and caspase-3.

γ‐aminobutyric acid‐mediated neurotransmission in cerebellar–hypothalamic circuit attenuates gastric mucosal injury induced by ischemia‐reperfusion

Excessive greater splanchnic nerve (GSN) activation contributes to the progression of gastric ischemia-reperfusion (GI-R) injury. This study was designed to investigate the protective mechanism of cerebellar fastigial nucleus (FN) stimulation against GI-R injury. The GI-R injury model was induced in rats by clamping the celiac artery for 30 min, and then reperfusion for 30 min, 1, 3, 6, or 24 h, respectively. Microinjection of L-Glu (3, 6, 12 μg) into the FN dose-dependently attenuated GI-R injury and GSN activity. In addition, there was an enhancement of gastric mucosal blood flow in GI-R rats. Pretreatment with the glutamic acid decarboxylase antagonist into the FN, the GABAA receptor antagonist into the lateral hypothalamic area or lesion of superior cerebellar peduncle all reversed the protective effects of the FN stimulation. Furthermore, the FN stimulation reduced the TUNEL-positive gastric mucosal cell and Bax-positive gastric mucosal cell in GI-R rats. These results indicate that the protective effects of the FN stimulation against GI-R injury may be mediated by attenuation of the excessive GSN activation, gastric mucosal cell apoptosis, and Bax expression in GI-R rats.

Protective effect of endogenous hydrogen sulfide against oxidative stress in gastric ischemia-reperfusion injury

Hydrogen sulfide (H2S) is a gaseous signaling molecule, which plays a critical role in a number of physiological and pathological progresses. In order to determine the effect of endogenous H2S on gastric ischemia-reperfusion (GI-R), we evaluated the gastric mucosal damage in rats intraperitoneally injected with DL-propargylglycine (PAG, 50 mg/kg/day) or L-cysteine (L-cys, 50 mg/kg/day) for 7 days before GI-R. GI-R injury was achieved by clamping the celiac artery for 30 min, followed by reperfusion for 60 min. Gastric mucosal damage was macroscopically assessed in the area of injury and deep damage was assessed by histopathological scoring. PAG increased the area of gastric mucosal injury and deep damage compared with that in untreated GI-R rats (P<0.05). While PAG decreased the H2S concentration and cystathionine γ-lyase (CSE) expression in the gastric mucosa, L-cys significantly attenuated the effects of GI-R. Western blot analysis revealed that the increases of malondialdehyde (MDA) and xanthine oxidase (XOD), and decreases of glutathione (GSH), superoxide dismutase (SOD) and the restriction of superoxide (O2−) production in the PAG group were inhibited by L-cys (P<0.05). Endogenous H2S has a protective effect against GI-R in rats by inhibiting oxygen free radical overproduction.

Lateral hypothalamic area mediated the protective effects of microinjection of glutamate into interpositus nucleus on gastric ischemia-reperfusion injury in rats

We investigated the protective effects of chemical stimulation of cerebellar interpositus nucleus (IN) on gastric ischemia-reperfusion injury (GI-RI) and its possible regulatory mechanisms in rats. Gastric mucosal damage index (GMDI) indicated the severity of gastric mucosal injuries. Transferase dUTP nick end labeling (TUNEL) staining and proliferating cell nuclear antigen (PCNA) were performed to assess gastric mucosal cell apoptosis and proliferation. Microinjection of glutamate into IN markedly attenuated GI-RI. Either chemical lesion of IN or electrical ablation of the decussation of superior cerebellar peduncle (DSCP) obviously aggravated GI-RI. The protective effects of IN were reversed with the pretreatments of microinjection of 3-mercaptopropionic acid into IN or Bicuculline into lateral hypothalamic area (LHA), individually. The discharge frequency and intensity of greater splanchnic nerve (GSN) decreased and gastric mucosal blood flow increased after chemical stimulation of IN. The apoptosis of positive cells of gastric mucosa was decreased by chemical stimulation of IN, whereas proliferation increased. The gastric juice volume, acidity, and total acid output were all decreased after the chemical stimulation of IN. These results indicated that IN participates in regulation of GI-RI and is a specific area in central nervous system for exerting protective effects on GI-RI. DSCP, LHA and GSN may involve in this process. Apoptosis and proliferation may mediate this protective process in rats too.

A preliminary study on protective effect of L-citrulline against ischemia-reperfusion induced gastric mucosal lesions in rat

Objectives:This study was designed to investigate the gastroprotective effect of L-citrulline against gastric ischemia-reperfusion injury.Materials and Methods:Sodium pentobarbital-anesthetized rats underwent occlusion of the celiac artery for 30 min, followed by 60 min of reperfusion. Sixty minutes before ischemia, L-citrulline at doses of 300, 600, 900 mg/kg was administered intragastrically. Based on this animal model of gastric ischemia-reperfusion injury, the gastroprotective effect of L-citrulline was assessed by determining and comparing the ulcerative index and the estimation of myeloperoxidase (MPO) activity and malondialdehyde (MDA) level in the gastric mucosal tissues. Moreover, the expression of inducible nitric oxide synthase (iNOS), neuronal nitric oxide synthase (nNOS), and endothelial nitric oxide synthase (eNOS) protein was also determined.Results:Intragastric administration of L-citrulline (600 and 900 mg/kg) 60 min before ischemia significantly ameliorated the gastric mucosal damage and inhibited the increase in MPO and MDA contents. Also, the increase in expression of iNOS protein was also prevented by L-citrulline. The expression of nNOS and eNOS was not affected significantly by I/R or L-citrulline.Conclusion:The results suggest that L-citrulline, administered exogenously, exhibits gastric protection by inhibition of neutrophil infiltration in rats, which may be related in prevention of the increase in iNOS activity.

Gastric peroxisome proliferator activator receptor-γ expression and cytoprotective actions of its ligands against ischemia-reperfusion injury in rats

The beneficial effects by peroxisome proliferator-activated receptor-γ (PPAR-γ) on gastric injury induced by ischemia-reperfusion have been confirmed, however, the precise mechanism of its cytoprotection is not elucidated thoroughly. The aim of the present study was to determine the gastric localization of PPAR-γ expression in the rat gastric mucosa, and to clarify the mechanism of its cytoprotective properties. The gastric expression of PPAR-γ was confirmed by RT-PCR and western blot, and localized on gastric epithelial cells. The protective effect of PPAR-γ ligands, pioglitazone or 15-deoxy-Δ12,14-prostaglandin J2, on gastric ischemia-reperfusion injury was reversed by the co-administration with PPAR-γ antagonist. The gastric expression of tumor necrosis factor-α and cytokine-induced neutrophil chemoattractant-1 increased significantly in rats treated ischemia-reperfusion, and these increases were significantly inhibited by treatment with pioglitazone. Among the 1,032 probes, 18 probes were up-regulated at least 1.5-fold, 17 were down-regulated at least 1.5-fold by pioglitazone. The network including calnexin, endoplasmic reticulum stress protein, heat shock proteins, and proteasome genes was induced by pioglitazone treatment. In conclusion, activation of gastric epithelial PPAR-γ receptor by its ligands may represent a novel therapeutic approach for gastric inflammation via up-regulation of heat shock proteins and endoplasmic reticulum-related proteins.

Protective effect of pantoloc against gastric ischemia-reperfusion injury is independent of Caspase-3 apoptosis pathway inhibition

The quorum sensing commonly exists in procaryote kingdom,regulating various biologic functions.Recently similar phenomenon was also found in fungi world,which affecting both biofilm formation and dimorphism.In this article,we focus on the recent progress on quorum sensing of pathogenic fungi and discuss the possibility of taking quorum sensing molecule as a potential target for antifungl therapy.

The protective effects of calcitonin gene-related peptide on gastric mucosa injury of gastric ischemia reperfusion in rats

Gastric mucosa is one of the most vulnerable tissues in human and animal. However, little is known about the effects of calcitonin gene-related peptide (CGRP) on gastric mucosa injuries induced by gastric ischemia reperfusion. The purpose of the present study was to investigate the protective effects and mechanism of CGRP on gastric mucosa injury after gastric ischemia reperfusion in rats. Thirty-six healthy Wistar rats were randomly divided into CGRP-treated, sham-operated, and control groups. Twelve rats were involved in each group. These groups were further divided into 24-h and 48-h subgroups. Gastric ischemia reperfusion injury (GI-RI) rat model was established by a 30-min celiac artery occlusion by an artery clamp, followed by 24 h or 48 h of reperfusion. CGRP (1 μg/ml) at the dose of 3 μg/kg was given intraperiloneally (IP) at the beginning of reperfusion for rats in CGRP-treated group. Saline as vehicle (3 ml/kg body weight), IP, was administered at the beginning of reperfusion for rats in control group. Sham-operated animals were subjected to an operation without GI-RI. Twenty-four hours or 48 h after operation, the samples were taken out and processed for calculating stomach mucous membrane damage index according to Guth method, detecting pathological changes of gastric mucosa tissue by light microscopy and observing the expression of gastrin (Gas) and somatostatin (SST) by immunohistochemical staining. The results showed the following: (i) gastric mucosa with diffuse edema, splinter hemorrhage and erosion, numerous endothelial cells necrosis, mucosa dissociation, and infiltration of inflammatory cells were observed in both control and CGRP-treated animals, especially in the earlier period (24 h) and then gradually healing. CGRP administration could reduce the damage of gastric mucosa. The injury index of gastric mucosa was lower in CGRP-treated group as compared with that in control group (P < 0.01). (ii) Gas expression in gastric antrum mucosa was lower in CGRP-treated group than that in control group (P < 0.01). SST expression in gastric antrum mucosa was higher in CGRP-treated group than that in control group (P < 0.01). It is concluded that CGRP regulated the secretion of Gas and SST and thus alleviated the damage of gastric mucosa induced by ischemia and reperfusion. CGRP might be a potential candidate for clinical therapy on modulating gastric mucosal protection and maintaining gastric mucosal integrity after ischemia and reperfusion of the stomach.

The Protective Effect of Capsaicin Receptor-Mediated Genistein Postconditioning on Gastric Ischemia–Reperfusion Injury in Rats

No published study has addressed the effect of genistein postconditioning on gastric ischemia-reperfusion (GI-R) injury in rats. To examine whether capsaicin receptor-mediated genistein postconditioning protects against gastric ischemia-reperfusion injury via the PI3K/Akt signal pathway. Chloraldurat-anesthetized rats underwent occlusion of the celiac artery for 30min, followed by 60min of reperfusion. Based on this animal model of gastric ischemia-reperfusion injury, genistein at doses of 100, 500 or 1,000μg/kg was administered via peripheral vein 5min before reperfusion. The dose of 500μg/kg was optimal for postconditioning, at which the severity of I-R-induced gastric injury significantly decreased. Immunohistochemistry also showed that gastric mucosal cell apoptosis decreased. Capsazepine (CPZ), a specific antagonist for the capsaicin receptor, was administered (1,000μg/kg, i.v.) just before ischemia. Capsaicin (50mg/kg, s.c.) once a day for 4days reversed the protective effects of genistein. Reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting showed increased calcitonin gene-related peptide (CGRP) expression in genistein group but not in capsazepine or capsaicin group. CGRP inhibitor CGRP8-37 also prevented the effects of genistein in decreasing gastric mucosal injury index. In addition, PI3K inhibitor LY294002 (1.5mg/kg) reversed the protective effect of genistein. Compared with genistein group, Western blots also demonstrated decreased Akt phosphorylation in LY294002 group. Our data suggest that capsaicin receptors mediated the protective effects of genistein postconditioning. CGRP secreted by activated capsaicin-sensitive neurons played an important role in the protective effects of genistein. PI3K/Akt pathway was also involved in the protective effects of genistein.

The role of nuclear factor-κB in the effect of angiotensin II in the paraventricular nucleus in protecting the gastric mucosa from ischemia-reperfusion injury in rats

The purpose of this study was to elucidate the role of nuclear factor kappaB (NF-kappaB) in the development of gastric ischemia-reperfusion (GI-R) injury and in mediating the effects of angiotensin II (Ang II) in the paraventricular nucleus (PVN) on GI-R injury. GI-R injury was induced in rats by clamping the celiac artery for 30 min and then reperfusing for 1 h. A cannula was inserted into the unilateral PVN for microinjection of Ang II. The expressions and levels of NF-kappaB (p65), IkappaB-alpha, and phosphorylated IkappaB-alpha in rat gastric mucosa were examined by Western blotting and immunohistochemistry. A laser Doppler flowmeter was used to assess gastric blood flow (GBF). Malondialdehyde (MDA) was determined using the thiobarbituric acid (TBA) method, and superoxide dismutase (SOD) activity was determined by the xanthine/xanthine oxidase method. Microinjection of Ang II (3, 30, and 300 ng) into the PVN dose-dependently inhibited GI-R injury. The levels and expressions of NF-kappaB (p65) and phosphospecific IkappaB-alpha protein increased 1 h after GI-R and were markedly reduced by microinjection of Ang II into the PVN. In contrast, the level and expression of IkappaB-alpha protein decreased 1 h after ischemia-reperfusion and recovered to the normal level by microinjection of Ang II into the PVN. The effects of Ang II were prevented by pretreatment with the Ang II AT1 receptor antagonist losartan (5 microg) microinjected into the lateral cerebral ventricle. Inhibition of NF-kappaB activity by pyrrolidine dithiocarbamate (PDTC, 200 mg/kg) produced similar effects in rats subjected to ischemia-reperfusion with or without microinjection of Ang II into the PVN. Administration of PDTC attenuated gastric mucosal injury and suppressed the activation of NF-kappaB (p65). Ang II microinjection into the PVN increased GBF and decreased the MDA content but did not alter SOD activity in the gastric mucosa following ischemia-reperfusion. NF-kappaB plays a role in PVN Ang II-mediated protection against GI-R injury. These central effects of Ang II are mediated by AT1 receptors.

Administration of angiotensin II in the paraventricular nucleus protects gastric mucosa from ischemia-reperfusion injury

Our previous study demonstrated that electrical stimulation of the hypothalamic paraventricular nucleus (PVN) protects against gastric ischemia-reperfusion (GI-R) injury, but it is still unknown whether angiotensin II (Ang II) in the PVN plays a role in the development of GI-R. The purpose of this study was to investigate the effect of Ang II in the PVN on GI-R injury. GI-R injury was induced in rats by clamping the celiac artery for 30 min, and then reperfusing for 30 min, 1 h, 3 h, 6 h or 24 h, respectively. A cannula was inserted into the unilateral PVN for microinjection of Ang II. The extent of gastric mucosal damage was determined by gross and histological methods. We found that microinjection of pharmacological doses of Ang II (3, 30, and 300 ng) into the PVN dose-dependently inhibited GI-R injury, and that Ang II (30 ng) markedly attenuated GI-R injury at 1 h and 3 h after reperfusion. The effect of Ang II was prevented by pretreatment with the Ang II AT1 receptor antagonist losartan (5 µg) into the lateral cerebral ventricle. Furthermore, the protective effect of Ang II on GI-R injury was abolished by propranolol (1 mg/kg, i.v.) or disconnection of the nerves innervating the adrenal glands, was augmented by sympathectomy or phentolamine (1 mg/kg, i.v.), and was not affected by subdiaphragmatic vagotomy or atropine (1 mg/kg, i.v.). These results indicate that the PVN is a responsive site for central Ang II-induced protection against GI-R injury. The central effects of Ang II are mediated by AT1 receptors in the PVN, and the peripheral effects by a sympathetic-adrenal gland/β-adrenoceptor pathway.

Capsaicin-sensitive afferent fibers mediate the protective effect of electrical stimulation of paraventricular nucleus against gastric ischemia-reperfusion injury in rats

Capsaicin-sensitive afferent fibers mediate the protective effect of electrical stimulation of paraventricular nucleus against gastric ischemia-reperfusion injury in rats