Important Role of Local Angiotensin II Activity Mediated via Type 1 Receptor in the Pathogenesis of Cardiovascular Inflammatory Changes Induced by Chronic Blockade of Nitric Oxide Synthesis in Rats

Usui, Makoto; Egashira, Kensuke; Tomita, Hideharu; Koyanagi, Masamichi; Katoh, Makoto; Shimokawa, Hiroaki; Takeya, Motohiro; Yoshimura, Teizo; Matsushima, Kouji; Takeshita, Akira

doi:10.1161/01.cir.101.3.305

Cited by 151 publications

(131 citation statements)

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“…In general, oxidative stress is considered to participate to the development of vascular inflammation (53,54). Previous studies (48, 54−56) have suggested that L-NAME treatment enhances oxidative stress in the aorta.…”

Section: Discussionmentioning

confidence: 99%

Calcium Channel Blockades Exhibit Anti-Inflammatory and Antioxidative Effects by Augmentation of Endothelial Nitric Oxide Synthase and the Inhibition of Angiotensin Converting Enzyme in the NG-Nitro-L-Arginine Methyl Ester-Induced Hypertensive Rat Aorta: Vasoprotective Effects beyond the Blood Pressure-Lowering Effects of Amlodipine and Manidipine

et al. 2005

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Section: Discussionmentioning

confidence: 99%

Calcium Channel Blockades Exhibit Anti-Inflammatory and Antioxidative Effects by Augmentation of Endothelial Nitric Oxide Synthase and the Inhibition of Angiotensin Converting Enzyme in the NG-Nitro-L-Arginine Methyl Ester-Induced Hypertensive Rat Aorta: Vasoprotective Effects beyond the Blood Pressure-Lowering Effects of Amlodipine and Manidipine

et al. 2005

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Section: Treatmentmentioning

confidence: 99%

“…This dose of olmesartan has no effect on AngII-induced increase in arterial pressure. 26 The fifth group (shamϩ7ND group, nϭ10) received physiological saline and intramuscular injections of pcDNA3-7ND plasmid DNA (100 g).In the shamϩ7ND, AngIIϩplasmid, and AngIIϩ7ND groups, transgene expression was enhanced by local intramuscular electroporation at the injection site immediately after the injection. Six 100-V, 50-ms electronic pulses were applied to each injection site using an Electroporator CUY21 (BTX).…”

mentioning

confidence: 99%

Monocyte Chemoattractant Protein-1 Is an Essential Inflammatory Mediator in Angiotensin II-Induced Progression of Established Atherosclerosis in Hypercholesterolemic Mice

Kitamoto

Ishibashi

et al. 2004

ATVB

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100

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Objective-Chronic inflammatory processes might be involved in the progression and destabilization of atherosclerotic plaques. Therefore, identification of the mechanism underlying arterial inflammatory function might lead to the development of novel therapeutic strategies. Angiotensin II (AngII) is implicated in atherogenesis by activating the vascular inflammation system, mainly through monocyte chemotaxis. Therefore, we hypothesized that AngII increases plaque size and promotes destabilization of established atheromas by activating the monocyte chemoattractant protein-1 (MCP-1) pathway. Methods and Results-We report here that 4-week infusion of AngII not only increased plaque size but also induced a destabilization phenotype (ie, increased macrophages and lipids and decreased collagen and smooth muscle cells) of pre-existing atherosclerotic lesions of hypercholesterolemic mice. AngII also enhanced the gene expression of inflammatory cytokines (TNF␣, etc.) and chemokines CCR2, etc Key Words: atherosclerosis Ⅲ hypercholesterolemia Ⅲ cell adhesion molecules Ⅲ inflammation Ⅲ gene therapy A therosclerosis and its complications are the major cause of death in Western countries. Recent evidence suggests that chronic inflammatory processes have an important role in atherosclerotic plaque progression, destabilization, and subsequent rupture/thrombosis, resulting in acute coronary syndrome and stroke. 1 Therefore, identification of the critical inflammatory pathway involved in plaque progression and destabilization of pre-existing established atheromas might aid in the development of novel therapeutic strategies to reduce atherothrombotic complications. Angiotensin II (AngII) is implicated in atherogenesis beyond its hemodynamic effects. 2 Infusion of AngII into hypercholesterolemic mice dramatically accelerates the development and/or progression of atherosclerotic lesions and the effects of AngII occurred independent of changes in arterial pressure or plasma lipid concentration. 3,4 The mechanism of AngII-induced enhancement of atherogenesis is probably multifactorial, and includes hemodynamic effects, endothelial dysfunction and activation, 5 oxidative stress, 6 and inflammation. 7,8 AngII increases monocyte chemotaxis, activates nuclear factor-B, and augments production of inflammatory cytokines and chemokines by arterial wall cells and monocytes. 9 -12 AngII is very important in the pathogenesis of atherothrombotic complications, as evidenced by clinical benefits of angiotensinconverting enzyme inhibition 13 and AngII receptor blockers. 14 There are no reports, however, that address the mechanism of AngII-induced enhancement of atherogenesis and plaque destabilization under in vivo conditions.Emerging evidence suggests that AngII activates cell inflammatory systems in arterial lesion. 1,2 Inflammatory changes in arterial lesions are characterized by the recruitment and activation of monocytes/macrophages, which are regulated by monocyte chemoattractant protein-1 (MCP-1). 15 Expression Vector7ND was constructed b...

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“…7 Treatment with ARBs leads to a decrease in inflammation and adhesion molecules, such as CRP, 8 intercellular adhesion molecule-1, chemokines, E-selectin and monocyte chemotactic protein (MCP)-1. 9,10 In addition, monocyte and endothelial cell activation markers were significantly decreased in patients with type 2 diabetes after treatment with valsartan. 11 In addition, valsartan has been shown to be effective at preventing coronary restenosis in an open-label clinical study (Val-PREST).…”

Section: Introductionmentioning

confidence: 99%

Safety and efficacy of antihypertensive therapy with add-on angiotensin II type 1 receptor blocker after successful coronary stent implantation

et al. 2009

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This study was performed to evaluate the safety and efficacy of additional antihypertensive therapy with angiotensin II type 1 receptor blocker (ARB; olmesartan or valsartan) after successful stent implantation in patients with coronary artery disease (CAD). Fifty patients with CAD after successful stent implantation were included in this study. They were divided into an ARB group, which initially received olmesartan (n¼20, 14±8 mg day À1 ) or valsartan (n¼20, 60±23 mg day À1 ) immediately after stent implantation, and a non-ARB group (n¼10) according to their blood pressure (BP). Follow-up coronary angiography, measurement of BP and blood sampling were performed before (at baseline) and 6-8 months after stent implantation (at follow-up). There were no significant differences in the baseline characteristics between the groups, except for BP. Although there were no changes in % diameter restenosis between the groups, the BP level in the ARB group at follow-up showed a significant reduction (125 ± 12/69 ± 9 mm Hg) and reached the target BP. There were no critical adverse effects in the ARB group throughout the study period. In addition, serum high-sensitive C-reactive protein (hs-CRP) and pentraxin 3 were significantly decreased in the ARB group but not in the non-ARB group. Although olmesartan and valsartan induced similar BP-lowering effects, olmesartan but not valsartan induced a significant decrease in hs-CRP, but did not increase serum uric acid. In conclusion, antihypertensive therapy with add-on low-dose ARB after stent implantation was safe and achieved the target BP. In particular, olmesartan had an anti-inflammatory effect.

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Important Role of Local Angiotensin II Activity Mediated via Type 1 Receptor in the Pathogenesis of Cardiovascular Inflammatory Changes Induced by Chronic Blockade of Nitric Oxide Synthesis in Rats

Cited by 151 publications

References 35 publications

Monocyte Chemoattractant Protein-1 Is an Essential Inflammatory Mediator in Angiotensin II-Induced Progression of Established Atherosclerosis in Hypercholesterolemic Mice

Safety and efficacy of antihypertensive therapy with add-on angiotensin II type 1 receptor blocker after successful coronary stent implantation

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