Sufentanil attenuates impairment of the endothelium-dependent vasodilation induced by hypoxia–reoxygenation in the rat coronary artery

2016 ◽  
Vol 94 (12) ◽  
pp. 1309-1314
Author(s):  
Xin-qi Cheng ◽  
Jun-yan Zhang ◽  
Shan-shan Gao ◽  
Hao Wu ◽  
You-mei Zuo ◽  
...  
Keyword(s):  
Sodium Nitroprusside ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Channel Blockers ◽  
Nitric Oxide Synthase Inhibitor ◽  
Dependent Protein ◽  
Coronary Tone ◽  
Synthase Inhibitor ◽  
Hypoxia Reoxygenation

Sufentanil has been used broadly in cardiac surgery, but the mechanisms by which it modulates coronary vascular tone after ischemia–reperfusion injury are largely unknown. Effects of sufentanil on coronary tone and on the relaxation of rat coronary arteries (CAs) in response to endothelium-dependent (acetylcholine) and endothelium-independent (sodium nitroprusside) relaxing agents in the presence of hypoxia–reoxygenation (H/R) was studied in an in vitro organ chamber setup. Sufentanil (10−7–10−4 mol/L) relaxed rat CA rings in endothelium-dependent and endothelium-independent manners. In endothelium-intact rings, preincubation of H/R-treated CAs with sufentanil (10−5 mol/L) significantly increased the acetylcholine response, but did not augment sodium nitroprusside-induced relaxation. Sufentanil-mediated potentiation of acetylcholine-induced relaxation was not affected by a nitric oxide synthase inhibitor or by intermediate- or small-conductance Ca2+-activated K+ channel blockers. However, potentiation was abolished by iberiotoxin (100 nmol/L), a selective inhibitor of large-conductance Ca2+-activated K+ channels, as well as Rp-cAMPS (30 μmol/L), a cyclic AMP-dependent protein kinase (PKA) inhibitor. Sufentanil induced endothelium-dependent and endothelium-independent relaxation and attenuated H/R-induced impairment of endothelium-dependent vasodilation in the rat CAs. The potentiating effect of sufentanil may involve activation of large-conductance Ca2+-activated K+ channels via cAMP-dependent mechanisms.

scholarly journals Protective Effect of Sodium Nitroprusside on the Rat Small Intestine Transplanted Mucosa

2015 ◽  
Vol 2015 ◽  
pp. 1-6
Author(s):  
Feng-Hua Chen ◽  
Ke Li ◽  
Lu Yin ◽  
Chun-Qiu Chen ◽  
Zhao-Wen Yan ◽  
...  
Keyword(s):  
Small Intestine ◽  
Molecular Markers ◽  
Protective Effect ◽  
Sodium Nitroprusside ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Small Bowel Transplantation ◽  
Mucosal Barrier ◽  
No Donor

The intestinal mucosal epithelium is extremely susceptible to even brief periods of ischemia. Mucosal barrier damage, which is associated with ischemia/reperfusion (I/R) injury and consequently bacterial translocation, remains a major obstacle for clinically successful small bowel transplantation (SBT). Previous studies have demonstrated a protective effect of nitric oxide (NO) on other transplanted organs and NO mediated intestinal protection has also been reportedin vitro. The aim of this study was to evaluate the effect of sodium nitroprusside (SNP), NO donor, on graft mucosal histology and molecular markers of function after SBT in rats. We used SNP in different period of heterotopic SBT rats. The groups consisted of SBT, pre-SNP group, and post-SNP group. Interestingly, the pre-SNP graft samples exhibited less damage compared to the SBT and post-SNP samples. In addition, mucosal samples from the pre-SNP group showed higher Na+-K+-ATPase activity and higher levels of laminin expression compared to the SBT and post-SNP samples. The findings of the present study reveal that SNP given before graft ischemia/reperfusion injury has a protective effect on mucosal histology and molecular markers of function in the transplanted small intestine.

scholarly journals Calcium/calmodulin-dependent protein kinase IV limits organ damage in hepatic ischemia-reperfusion injury through induction of autophagy

2012 ◽  
Vol 303 (2) ◽  
pp. G189-G198 ◽  
Author(s):  
John Evankovich ◽  
Ruilin Zhang ◽  
Jon S. Cardinal ◽  
Lemeng Zhang ◽  
Junda Chen ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Knockout Mice ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Organ Damage ◽  
Dependent Protein Kinase ◽  
Hepatic Ischemia ◽  
Calcium Calmodulin Dependent ◽  
Dependent Protein

Sterile inflammatory insults, such as ischemia-reperfusion (I/R) injury, result from pathogenic factors, including damage-associated molecular pattern signaling, activation of innate immunity, and upregulation of proinflammatory cytokines. At the same time, a number of protective, or prosurvival, pathways are also activated, and the extent of end-organ damage is ultimately determined by the balance between these two systems. In liver I/R, members of the calcium/calmodulin-dependent protein kinase (CaMK) family are known to be activated, but their individual roles are largely unknown. In this study, we show that one CaMK member, CaMKIV, is protective in hepatic I/R by activating the prosurvival pathway of autophagy in hepatocytes. CaMKIV knockout mice experience significantly worse organ damage after I/R and are deficient in hepatocyte autophagic signaling. Restoration of autophagic signaling with rapamycin reduces organ damage in CaMKIV knockout mice to wild-type levels. In vitro, we show that CaMKIV activation induces autophagy in mouse hepatocytes, and that CaMKIV activation protects hepatocytes from oxidative stress-induced cell death. In conclusion, the protective autophagic signaling pathway serves to reduce organ damage following I/R and is regulated by activation of CaMKIV signaling in hepatocytes.

scholarly journals Adiponectin prevents islet ischemia–reperfusion injury through the COX2–TNFα–NF-κB-dependent signal transduction pathway in mice

2013 ◽  
Vol 218 (1) ◽  
pp. 75-84 ◽  
Author(s):  
Xiaojiong Du ◽  
Sirong He ◽  
Yaowen Jiang ◽  
Lingling Wei ◽  
Weiming Hu
Keyword(s):  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Islet Cells ◽  
Ischemia Reperfusion ◽  
Protective Action ◽  
Islet Transplants ◽  
Transplant Procedure ◽  
Hypoxia Reoxygenation

Islets are exceptionally susceptible to ischemia–reperfusion injury, an increased incidence of primary graft nonfunctionality, and β-cell death during a transplant procedure. Therefore, islets require protection during the early stages of the transplant procedure. Based on the beneficial vascular and anti-inflammatory activity of adiponectin, we hypothesize that adiponectin protects islet cells against ischemia–reperfusion injury and graft dysfunction after transplantation. To examine the effects of adiponectin on the resistance of islet ischemia–reperfusion injury, we used the islet hypoxia–reoxygenation injury model and performed kidney subcapsular syngeneic islet transplants to assess the islets' vitality and function. Furthermore, we utilized lipopolysaccharide (LPS)-induced or tumor necrosis factor α (TNFα)-induced damage to islet cells to model the inflammation of post-transplant ischemia–reperfusion injury and transplanted islets in adiponectin knockout mice to explore whether the protective action of adiponectin is involved in TNFα production and nuclear transcription factor-κB (NF-κB) activation. Adiponectin suppressed TNFα production and IκB-α phosphorylation; decreased hypoxia–reoxygenation and LPS-induced and TNFα-induced islet apoptosis; and improved islet function in vivo and in vitro. Our results demonstrate that adiponectin protects the islet from injury. We show that islet protection occurs in response to ischemia–reperfusion and is dependent on the suppression of islet production by TNFα through cyclooxygenase 2 and the inhibition of the TNFα-induced NF-κB activation pathways.

scholarly journals (Pro)renin Receptor Contributes to Hypoxia/Reoxygenation-Induced Apoptosis and Autophagy in Myocardial Cells via the β-Catenin Signaling Pathway

2020 ◽  
pp. 427-438
Author(s):  
X GAO ◽  
S ZHANG ◽  
D WANG ◽  
Y CHENG ◽  
Y JIANG ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Cell Counting ◽  
H9c2 Cells ◽  
Related Factors ◽  
Myocardial Ischemia Reperfusion ◽  
Induced Apoptosis ◽  
Hypoxia Reoxygenation

(Pro)renin receptor (PRR) contributes to regulating many physiological and pathological processes; however, the role of PRR-mediated signaling pathways in myocardial ischemia/reperfusion injury (IRI) remains unclear. In this study, we used an in vitro model of hypoxia/reoxygenation (H/R) to mimic IRI and carried out PRR knockdown by siRNA and PRR overexpression using cDNA in H9c2 cells. Cell proliferation activity was examined by MTT and Cell Counting Kit-8 (CCK-8) assays. Apoptosis-related factors, autophagy markers and β-catenin pathway activity were assessed by real-time PCR and western blotting. After 24 h of hypoxia followed by 2 h of reoxygenation, the expression levels of PRR, LC3B-I/II, Beclin1, cleaved caspase-3, cleaved caspase-9 and Bax were upregulated, suggesting that apoptosis and autophagy were increased in H9c2 cells. Contrary to the effects of PRR downregulation, the overexpression of PRR inhibited proliferation, induced apoptosis, increased the expression of pro-apoptotic factors and autophagy markers, and promoted activation of the β-catenin pathway. Furthermore, all these effects were reversed by treatment with the β-catenin antagonist DKK-1. Thus, we concluded that PRR activation can trigger H/R-induced apoptosis and autophagy in H9c2 cells through the β-catenin signaling pathway, which may provide new therapeutic targets for the prevention and treatment of myocardial IRI.

scholarly journals Mir10a overexpression aggravates the renal ischemia-reperfusion injury associated with a decrease in PIK3CA

2020 ◽  
Author(s):  
Dongsheng Xu ◽  
Wenjun Li ◽  
Tao Zhang ◽  
Gang Wang
Keyword(s):  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Luciferase Reporter ◽  
Akt Pathway ◽  
Luciferase Reporter Gene ◽  
Gene Assay ◽  
Underlying Mechanisms ◽  
Related Proteins ◽  
Hypoxia Reoxygenation

Abstract Background: To investigate the effect of miR-10a on the renal tissues with ischemia-reperfusion (I/R) injury in rats and explore the underlying mechanisms of miR-10a in the HK-2 cells of hypoxia-reoxygenation. Methods: The miR-10a level was measured in renal tissues with I/R rats by RT-PCR. In order to research the role of miR-10a in the renal tissues, miR-10 agonist and miR-10a antagonist were used to treat I/R rats. The levels of serum creatinine (Scr) and blood urea nitrogen (BUN) in serum, renal histopathology, apoptosis of cells in renal tissues were analyzed, separately. The phosphatidylinositol 3-kinase (PI3K)/Akt pathway related proteins were measured by Western blot. The HK-2 cell was cultured to study the mechanism of miR-10a in the model of hypoxia-reoxygenation. The dual luciferase reporter gene assay was used to confirm the PI3K p100 catalytic subunit α (PIK3CA) was a target gene of miR-10a. Results: After renal I/R injury in rats, the miR-10a expression was significantly increased (p<0.05). Injection of miR-10a agonist significantly aggravated the injury of renal and raised the apoptosis of cells in renal in rats with renal I/R injury (p<0.05). However, administration of miR-10a antagonist obviously improved the injury of renal, decreased the renal cells apoptosis and inhibited the PI3K/Akt pathway activity (p<0.05). In vitro experiments, the negative relation between PIK3CA and miR-10a was confirmed. Further, overexpression of miR-10a significantly decreased the proliferation of HK-2 cells, and increased the cells apoptosis via up-regulating PI3K/Akt pathway (p<0.05). Conclusion: miR-10a could aggravate the renal I/R injury associated with a decrease in PIK3CA/PI3K/Akt pathway.

scholarly journals NMDA Receptor-mediated CaMKII/ERK Activation Contributes to Renal Fibrosis

2020 ◽  
Author(s):  
Jingyi Zhou ◽  
Shuaihui Liu ◽  
Luying Guo ◽  
Rending Wang ◽  
Jianghua Chen ◽  
...  
Keyword(s):  
Western Blot ◽  
Renal Fibrosis ◽  
Ischemia Reperfusion Injury ◽  
Lentiviral Vector ◽  
Ischemia Reperfusion ◽  
Erk Activation ◽  
Function Impairment ◽  
Dependent Protein

Abstract Background: Renal fibrosis (RF) results in renal function impairment and eventually kidney failure. We found that N-methyl-D-aspartate receptor (NMDAR) played an important role during RF. However, its mechanism of action is yet to be deciphered. Methods: Acute RF was induced in mice by unilateral ureteral obstruction (UUO). NR1, which is the functional subunit of NMDAR, was downregulated using lentiviral vector-mediated shRNA interference. Histological changes were observed by Masson’s trichrome staining. Expression of NR1, fibrotic and EMT markers were measured by immunohistochemistry and western blot analysis. HK-2 cells were incubated with TGF-β, and NMDAR antagonist MK-801 and Ca2+/calmodulin-dependent protein kinase II (CaMKII) antagonist KN-93 administration were further included in this study for pathway determination. Expression of NR1, total and phosphorylated CaMKII, total and phosphorylated ERK were measured using western blot and immunofluorescent assays. Chronic renal fibrosis was introduced by sublethal ischemia-reperfusion injury in mice, and oral NMDAR inhibitor dextromethorphan (DXM) administration was performed. Results: NR1 expressions were upregulated in both obstructed kidneys and TGF-β treated HK-2 cells. NR1 knockdown, MK801 and KN93 reduced the fibrotic morphology in vivo and in vitro respectively, and companied with the downregulated ERK activation, while KN93 administration had no effect on NR1 and CaMKII levels. Mice in the DXM group had better preservation of kidney structures and corticomedullary volumes. Conclusions: NMDAR participates in both acute and chronic renal fibrogenesis via CaMKII/ERK activation, and is a potential therapeutic target for renal fibrosis.

scholarly journals DHA Attenuates Hypoxia/Reoxygenation Injury by Activating SSeCKS in Human Cerebrovascular Pericytes

2019 ◽  
Vol 45 (2) ◽  
pp. 310-321
Author(s):  
Yanli Yu ◽  
Haibin Fang ◽  
Zhen Qiu ◽  
Zhongyuan Xia ◽  
Bin Zhou
Keyword(s):  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Cell Junctions ◽  
Cell Permeability ◽  
Vegf Expression ◽  
Cerebral Ischemia Reperfusion Injury ◽  
Ldh Release ◽  
Underlying Mechanisms ◽  
Hypoxia Reoxygenation

AbstractDocosahexaenoic acid (DHA) can alleviate cerebral ischemia/reperfusion injury by reducing blood–brain barrier permeability and maintaining its integrity, accompanied by an increased Ang-1/Ang-2 ratio; however, the underlying mechanisms of these effects remain unclear. Src-suppressed C kinase substrates (SSeCKS), a substrate of protein kinase C, plays an important role in maintaining cell junctions and cell morphology and regulating cell permeability. However, whether DHA can increase SSeCKS expression and then mediate the Ang-1/Ang-2 ratio still needs to be studied. Human cerebrovascular pericytes (HBVPs) cultured in vitro were divided into groups, treated with or without DHA along with SSeCKS siRNA to knockdown SSeCKS expression, and then subjected to 24 h of hypoxia followed by 6 h of reoxygenation. Cell viability; lactate dehydrogenase (LDH) release; and Ang-1, Ang-2 and VEGF activity were detected by using ELISA kits. The apoptosis rate was assessed by TUNEL flow cytometry. Expression of the SSeCKS, Ang-1, Ang-2 and VEGF proteins was evaluated by western blotting. Pretreatment with 10 μM or 40 μM DHA efficiently attenuated hypoxia/reoxygenation (H/R) injury by activating SSeCKS to increase the Ang-1/Ang-2 ratio and downregulate VEGF expression in HBVPs, as evidenced by decreased LDH release and apoptotic rates and increased HBVPs viability. Meanwhile, after we used SSeCKS siRNA to knock down SSeCKS protein expression, the protective effect of DHA on HBVPs following H/R injury was reversed. In conclusion, DHA can activate SSeCKS to increase the Ang-1/Ang-2 ratio and downregulate VEGF expression in HBVPs, thus reducing H/R injury.

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