scholarly journals Angiotensin II Removes Kidney Resistance Conferred by Ischemic Preconditioning

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Hee-Seong Jang ◽  
Jee In Kim ◽  
Jinu Kim ◽  
Jeen-Woo Park ◽  
Kwon Moo Park
Keyword(s):  
Oxidative Stress ◽  
Angiotensin Ii ◽  
Ischemic Preconditioning ◽  
Inflammatory Responses ◽  
Ischemia Reperfusion ◽  
Sham Operation ◽  
Kidney Fibrosis ◽  
Losartan Treatment

Ischemic preconditioning (IPC) by ischemia/reperfusion (I/R) renders resistance to the kidney. Strong IPC triggers kidney fibrosis, which is involved in angiotensin II (AngII) and its type 1 receptor (AT1R) signaling. Here, we investigated the role of AngII/AT1R signal pathway in the resistance of IPC kidneys to subsequent I/R injury. IPC of kidneys was generated by 30 minutes of bilateral renal ischemia and 8 days of reperfusion. Sham-operation was performed to generate control (non-IPC) mice. To examine the roles of AngII and AT1R in IPC kidneys to subsequent I/R, IPC kidneys were subjected to either 30 minutes of bilateral kidney ischemia or sham-operation following treatment with AngII, losartan (AT1R blocker), or AngII plus losartan. IPC kidneys showed fibrotic changes, decreased AngII, and increased AT1R expression. I/R dramatically increased plasma creatinine concentrations in non-IPC mice, but not in IPC mice. AngII treatment in IPC mice resulted in enhanced morphological damage, oxidative stress, and inflammatory responses, with functional impairment, whereas losartan treatment reversed these effects. However, AngII treatment in non-IPC mice did not change I/R-induced injury. AngII abolished the resistance of IPC kidneys to subsequent I/R via the enhancement of oxidative stress and inflammatory responses, suggesting that the AngII/AT1R signaling pathway is associated with outcome in injury-experienced kidney.

Angiotensin II type 1 receptor blocker preserves tolerance to ischemia-reperfusion injury in Dahl salt-sensitive rat heart

2008 ◽  
Vol 294 (6) ◽  
pp. H2473-H2479 ◽  
Author(s):  
Seiji Matsuhisa ◽  
Hajime Otani ◽  
Toru Okazaki ◽  
Koji Yamashita ◽  
Yuzo Akita ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Angiotensin Ii ◽  
Nitric Oxide Synthase ◽  
Infarct Size ◽  
Rat Heart ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Oxide Synthase

Oxidative stress is involved in the tolerance to ischemia-reperfusion (I/R) injury. Because angiotensin II type 1 receptor blockers (ARBs) inhibit oxidative stress, there is concern that ARBs abolish the tolerance to I/R injury. Dahl salt-sensitive (DS) hypertensive and salt-resistant (DR) normotensive rats received an antioxidant, 2-mercaptopropionylglycine (MPG), or an ARB, losartan, for 7 days. Losartan and MPG significantly inhibited oxidative stress as determined by tissue malondialdehyde + 4-hydroxynoneal and increased expression of inducible nitric oxide synthase (iNOS) in the DS rat heart. However, losartan but not MPG activated endothelial nitric oxide synthase (eNOS) as assessed by phosphorylation of eNOS on Ser1177. Infarct size after 30-min left coronary artery occlusion followed by 2-h reperfusion was comparable between DS and DR rat hearts. Although MPG and losartan had no effect on infarct size in the DR rat heart, MPG but not losartan significantly increased infarct size in the DS rat heart. A selective iNOS inhibitor, 1400W, increased infarct size in the DS rat heart, but it had no effect on infarct size in the losartan-treated DS rat heart. However, a nonselective NOS inhibitor, Nω-nitro-l-arginine methyl ester, increased infarct size in the losartan-treated DS rat heart. These results suggest that losartan preserves the tolerance to I/R injury by activating eNOS despite elimination of redox-sensitive upregulation of iNOS and iNOS-dependent cardioprotection in the DS rat heart.

Angiotensin II type 1 receptors and the intestinal microvascular dysfunction induced by ischemia and reperfusion

2006 ◽  
Vol 290 (6) ◽  
pp. G1203-G1210 ◽  
Author(s):  
Thomas Petnehazy ◽  
Dianne Cooper ◽  
Karen Y. Stokes ◽  
Janice Russell ◽  
Katherine C. Wood ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Bone Marrow ◽  
Angiotensin Ii ◽  
Blood Cell ◽  
Blood Cells ◽  
Platelet Adhesion ◽  
Sham Operation ◽  
Cell Recruitment ◽  
Bone Marrow Chimeras

The acute phase of intestinal ischemia-reperfusion (I/R) injury is mediated by leukocytes and is characterized by oxidative stress and blood cell recruitment. Upregulation of angiotensin II type 1 receptors (AT1-R) has been implicated in the pathogenesis of conditions associated with oxidative stress. The AT1-R-antagonist Losartan (Los) attenuates leukocyte recruitment following I/R. However, the role of AT1-R in intestinal I/R injury and the associated platelet-leukocyte interactions remains unclear. The objective of this study was to define the contribution of AT1-R to I/R-induced blood cell recruitment in intestinal venules. Leukocyte and platelet adhesion were quantified by intravital microscopy in the small bowel of C57Bl/6 [wild-type (WT)] mice exposed to sham operation or 45 min of ischemia and 4 h of reperfusion. A separate WT group received Los for 7 days before gut I/R (WT-I/R + Los). AT1-R bone marrow chimeras that express AT1-R on the vessel wall but not blood cells also underwent I/R. Platelet and leukocyte adhesion as well as AT1-R expression in the gut microvasculature were significantly elevated after I/R. All of these responses were attenuated in the WT-I/R + Los group, compared with untreated I/R mice. A comparable abrogation of I/R-induced blood cell adhesion was noted in AT1-R bone marrow chimeras. I/R-induced platelet adhesion was unaltered in mice overexpressing Cu,Zn-SOD or mice deficient in NAD(P)H oxidase. These data suggest that although gut I/R upregulates endothelial expression of AT1-R, engagement of these angiotensin II receptors on blood cells is more important in eliciting the prothrombogenic and proinflammatory state observed in postischemic gut venules, through a superoxide-independent pathway.

scholarly journals The Role of SIRT3 in Mediating Cardioprotective Effects of RAS Inhibition on Cardiac Ischemia-Reperfusion

2015 ◽  
Vol 18 (3) ◽  
pp. 547 ◽  
Author(s):  
Sabzali Javadov ◽  
Nelson Escobales
Keyword(s):  
Angiotensin Ii ◽  
Molecular Mechanisms ◽  
Ischemia Reperfusion ◽  
Renin Angiotensin System ◽  
Cardiac Ischemia ◽  
Pharmaceutical Sciences ◽  
Ras Inhibition ◽  
Cardioprotective Effects

Cardiac ischemia-reperfusion stimulates the renin-angiotensin system (RAS) associated with elevated levels of circulating angiotensin II. Numerous studies demonstrate that the antagonist for the angiotensin II type 1 receptor, losartan improves cardiac function in animal models of ischemia-reperfusion. Molecular mechanisms of the cardioprotective effects of RAS inhibitors on cardiac ischemia-reperfusion remain poorly understood, and are not associated with the anti-hypertensive action of these drugs. This Commentary focuses on the study published in the Journal of Pharmacy and Pharmaceutical Sciences, 2015, 18:112-123, that elucidates the role of SIRT3 in the cardioprotective action of losartan against ischemic-reperfusion injury. We provide comprehensive discussion of the role of mitochondria in the cardioprotective effects of losartan through SIRT3. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

scholarly journals Role of Platelet Activation and Oxidative Stress in the Evolution of Myocardial Infarction

2019 ◽  
Vol 24 (6) ◽  
pp. 509-520 ◽  
Author(s):  
Eduardo Fuentes ◽  
Rodrigo Moore-Carrasco ◽  
Antonio Marcus de Andrade Paes ◽  
Andres Trostchansky
Keyword(s):  
Oxidative Stress ◽  
Myocardial Infarction ◽  
Reperfusion Injury ◽  
Antiplatelet Therapy ◽  
Inflammatory Responses ◽  
Ischemia Reperfusion Injury ◽  
Coronary Thrombosis ◽  
Ischemia Reperfusion ◽  
Critical Role

Myocardial infarction, commonly known as heart attack, evolves from the rupture of unstable atherosclerotic plaques to coronary thrombosis and myocardial ischemia–reperfusion injury. A body of evidence supports a close relationship between the alterations following an ischemia–reperfusion injury-induced oxidative stress and platelet activity. Through their critical role in thrombogenesis and inflammatory responses, platelets are fully (totally) implicated from atherothrombotic plaque formation to myocardial infarction onset and expansion. However, mere platelet aggregation prevention does not offer full protection, suggesting that other antiplatelet therapy mechanisms may also be involved. Thus, the present review discusses the integrative role of platelets, oxidative stress, and antiplatelet therapy in triggering myocardial infarction pathophysiology.

The possible protective effect of colchicine against liver damage induced by renal ischemia–reperfusion injury: role of Nrf2 and NLRP3 inflammasome

2020 ◽  
Vol 98 (12) ◽  
pp. 849-854
Author(s):  
Azza Sayed Awad ◽  
Hemat A. Elariny ◽  
Amany Said Sallam
Keyword(s):  
Oxidative Stress ◽  
Liver Injury ◽  
Protective Effect ◽  
Reperfusion Injury ◽  
Nlrp3 Inflammasome ◽  
Inflammatory Responses ◽  
Ischemia Reperfusion Injury ◽  
Tissue Injury ◽  
Ischemia Reperfusion ◽  
Sham Operation

Ischemia–reperfusion injury (IRI) induces an inflammatory response and production of reactive oxygen species, which affects the organs remote to the sites of renal IR. However, remote effects of renal IRI on the liver need further investigations. Renal injury associated with liver disease is a common clinical problem. Colchicine is an established drug for microtubule stabilization that may reduce tissue injury and has antioxidant and antiinflammatory effects. The aim of the present study was (i) to assess the hepatic changes after induction of renal IRI, (ii) to explore the possible protective effect of colchicine on liver injury following renal IRI, and (iii) to investigate the possible mechanisms underlying the potential effect. Forty rats were randomly divided into four groups: sham operation group, colchicine-treated group, IR group, and colchicine-treated IR group. Colchicine treatment improved liver function (ALT/AST) after renal IRI, decreased hepatic oxidative stress and cell apoptosis by reducing hepatic MDA, upregulating hepatic total antioxidant capacity, Nrf2, and HO-1. Furthermore, colchicine inhibited inflammatory responses by downregulating hepatic NLRP3 inflammasome, IL-1β, and caspase-1. Colchicine attenuates renal IRI-induced liver injury in rats. This effect may be due to reducing inflammation and oxidative stress markers.

Abstract 086: Adenosine A3 Receptors Regulate Oxidative Stress And Inflammatory Responses In A Model Of Hypertension And Renal Disease

Hypertension ◽  
2014 ◽  
Vol 64 (suppl_1) ◽  
Author(s):  
Ting Yang ◽  
Micheal Hezel ◽  
Maria Peleli ◽  
Xingmei Zhang ◽  
Niccolo Terrando ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Blood Pressure ◽  
Inflammatory Responses ◽  
Renal Plasma Flow ◽  
Disease Model ◽  
Sham Operation ◽  
High Salt Diet ◽  
Renal Autoregulation ◽  
Cytokine Levels

BACKGROUND: Adenosine A1 and A2 receptors are known to regulate renal autoregulation and blood pressure, but the role of A3 signaling is unknown. We previously demonstrated early life reduction in nephron number (UNX) combined with high salt diet (HS) induced renal oxidative stress and hypertension in rats. This study aimed at investigating the role of A3 receptor in modulating renal and cardiovascular function in this disease model. METHODS: Wild-type (WT) and A3 knockout (A3KO) mice underwent UNX or sham-operation at 3-week-age followed by HS treatment. Blood pressure and renal function were measured in conscious aged mice and renal oxidative stress as well as inflammatory properties was characterized. RESULTS: WT but not A3KO with UNX+HS developed hypertension and cardiac hypertrophy (WT: 4.5±0.1 vs 4.0±0.1; A3KO: 4.7±0.2 vs 4.6±0.1 mg/gBW), characterized by impaired renal plasma flow (RPF), glomerular hyperfiltration and increased renal NADPH oxidase activity (Fig. 1A-C). UNX+HS increased plasma IL-6 (36.1±5.7 vs 16.3±2.4 pg/ml) and IL-10 (37.8±3.9 vs 25.4±2.4 pg/ml) levels in WT, but not in A3KO (39.7±3.9 vs 38.5±5.9 pg/ml and 46.5±3.7 vs 43.9±6.0 pg/ml respectively). However, A3KO displayed higher baseline cytokine levels. Furthermore, bone marrow-derived macrophages from A3KO mice expressed higher M1 (PDL-1 and CD86) and M2 (PDL2 and CD206) markers under LPS stimulation compared with WT. These suggested an enhanced innate immune response in A3KO. CONCLUSION: UNX followed by HS intake lead to renal and cardiovascular dysfunction, which importantly depends on A3 receptor-mediated regulation of oxidative stress and inflammation.

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