Chronic Production of Peroxynitrite in the Vascular Wall Impairs Vasorelaxation Function in SHR/NDmcr-cp Rats, an Animal Model of Metabolic Syndrome
スポンサーリンク
概要
- 論文の詳細を見る
We have previously reported that peroxynitrite is involved in dysfunction of nitric oxide (NO)-mediated vasorelaxation in SHR/NDmcr-cp rats (SHR-cp), which display typical symptoms of metabolic syndrome. This study investigated whether peroxynitrite is actually generated in the vascular wall with angiotensin II–induced NADPH-oxidase activation, thus contributing to the dysfunction. In isolated mesenteric arteries of male 18-week-old SHR-cp, relaxations in response to acetylcholine and sodium nitroprusside were impaired compared with that in Wistar-Kyoto rats. This impaired relaxation was not restored by treatment with apocynin, an NADPH-oxidase inhibitor. Protein expression of endothelial NO synthase increased while that of soluble guanylyl cyclase (sGC) decreased in the artery. We observed increased production of superoxide anions and peroxynitrite from the artery and their inhibition by apocynin, and also increased contents of nitrotyrosine, a biomarker of peroxynitrite, in mesenteric arteries and angiotensin II in aortas. Long-term (8 weeks) administration of telmisartan, an angiotensin II type 1–receptor antagonist, prevented the impaired vasorelaxation, decreased sGC expression and increased nitrotyrosine content in mesenteric arteries. These findings suggest that in the vascular wall of SHR-cp, peroxynitrite is continually produced by the reaction of NO with NADPH oxidase–derived superoxide via angiotensin II and gradually denatures sGC protein, leading to vasorelaxation dysfunction.
- 社団法人 日本薬理学会の論文
- 2009-04-20
著者
-
Nakamura Katsuya
Medicinal Chemistry Research Laboratories Fujisawa Pharmaceutical Co. Ltd.
-
KAGOTA Satomi
Department of Pharmacology, School of Pharmaceutical Sciences, Mukogawa Women's University
-
NAKAMURA Kazuki
Department of Pharmacology, School of Pharmaceutical Sciences, Mukogawa Women's University
-
KUNITOMO Masaru
Department of Pharmacology, School of Pharmaceutical Sciences, Mukogawa Women's University
-
SHINOZUKA Kazumasa
Department of Pharmacology, School of Pharmaceutical Sciences, Mukogawa Women's University
-
Nakamura K
Department Of Pharmacology School Of Pharmacy And Pharmaceutical Sciences Mukogawa Women's Univ
-
Kunimoto M
Department Of Pharmacology School Of Pharmacy And Pharmaceutical Sciences Mukogawa Women's Univ
-
Kunitomo Masaru
京都大学 医学研究科糖尿病･栄養内科学
-
TADA Yukari
Department of Pharmacology, School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women's Univers
-
NEJIME Namie
Department of Pharmacology, School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women's Univers
-
Nakamura Kazufumi
Faculty Of Pharmaceutical Sciences Kyushu University
-
Kunitomo Masaru
Department Of Pharmacology Faculty Of Pharmaceutical Sciences Mukogawa Women's University
-
Kunitomo Masaru
Department Of Pharmacology Shizuoka College Of Pharmaceutical Science
-
Nakamura Kazuki
Department Of Applied Chemistry Faculty Of Engineering Shibaura Institute Of Technology
-
Nakamura Katsuji
Tsukuba Research Laboratories Eisai Co. Ltd.
-
Shinozuka Kazumasa
Department Of Pharmacology School Of Pharmacy And Pharmaceutical Sciences Mukogawa Women's Univ
-
Shinozuka Kazumasa
Dep. Of Pharmacology School Of Pharmacy And Pharmaceutical Sciences Mukogawa Women's Univ. Jpn
-
Shinozuka Kazumasa
Department Of Pharmacology Shizuoka College Of Pharmaceutical Sciences
-
Shinozuka Kazumasa
Department Of Pharmacology Faculty Of Pharmaceutical Science Mukogawa Women's University
-
Nakamura K
Department Of Physiology Ii Iwate Medical University School Of Medicine
-
Shinozuka K
Department Of Pharmacology School Of Pharmacy And Pharmaceutical Sciences Mukogawa Women's Univ
-
Kagota Satomi
Department Of Pharmacology Faculty Of Pharmaceutical Sciences Mukogawa Women's University
-
Kunitomo Masaru
Dep. Of Pharmacology School Of Pharmaceutical Sciences Mukogawa Women's Univ. Jpn
-
Saito K
School Of Pharmacy And Pharmaceutical Sciences Mukogawa Women's University
-
Tanioka Y
Department Of Pharmacology School Of Pharmacy And Pharmaceutical Sciences Mukogawa Women's University
-
Tada Yukari
Department of Pharmacology, School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women's University
-
Nejime Namie
Department of Pharmacology, School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women's University
-
Shinozuka Kazumasa
Department of Applied Chemistry, Faculty of Engineering, Yokohama National University
-
Nejime Namie
Department of Pharmacology, School of Pharmaceutical Sciences, Mukogawa Women's University
関連論文
- Effects of Dietary Ingredients on Function and Expression of P-Glycoprotein in Human Intestinal Epithelial Cells
- Characterization of cardiac size and function in SHRSP.Z-Lepr[fa]/IzmDmcr rats, a new animal model of metabolic syndrome
- Evaluation of Blood Pressure Measured by Tail-Cuff Methods (without Heating) in Spontaneously Hypertensive Rats(Pharmacology)
- Effects of Ginkgo Biloba Extract Feeding on Salt-Induced Hypertensive Dahl Rats(Pharmacology)
- Safety of Dietary Supplements:Chronotropic and Inotropic Effects on Isolated Rat Atria
- Biochemical Evidence of Atherosclerosis Progression Mediated by Increased Oxidative Stress in Apolipoprotein E-Deficient Spontaneously Hyperlipidemic Mice Exposed to Chronic Cigarette Smoke
- Chronic Production of Peroxynitrite in the Vascular Wall Impairs Vasorelaxation Function in SHR/NDmcr-cp Rats, an Animal Model of Metabolic Syndrome
- Long-Term Feeding of Ginkgo biloba Extract Impairs Peripheral Circulation and Hepatic Function in Aged Spontaneously Hypertensive Rats(Pharmacognosy)
- P2Y Receptor-Mediated Ca^ Signaling Increases Human Vascular Endothelial Cell Permeability
- Pharmacology and Physiology of Perivascular Nerves Regulating Vascular Function : Purinergic Modulation of Vascular Sympathetic Neurotransmission
- Characterization of Prejunctional Purinoceptors Inhibiting Noradrenaline Release in Rat Mesenteric Arteries
- Activation of In Vivo Kupffer Cell Function by Oral Administration of Cordyceps sinensis in Rats
- Inhibitory Effect of Cordyceps sinensis on Spontaneous Liver Metastasis of Lewis Lung Carcinoma and B16 Melanoma Cells
- Beneficial Effect of Coenzyme Q10 on Increased Oxidative and Nitrative Stress and Inflammation and Individual Metabolic Components Developing in a Rat Model of Metabolic Syndrome
- Anion-exchange high-performance liquid chromatography assays of plasma lipoproteins and modified low-density lipoproteins using a ProtEx-DEAE column
- Peroxynitrite-Generating Species: Good Candidate Oxidants in Aqueous Extracts of Cigarette Smoke
- High-performance liquid chromatographic assay of hydroperoxide levels in oxidatively modified lipoproteins
- Anion-exchange high-performance liquid chromatographic assay of plasma lipoproteins of rabbits, rats and mice
- Regional Differences in Noradrenaline-Induced Release of Adenosine Triphosphate from Rat Vascular Endothelium
- Characterization of Cardiac Size and Function in SHRSP.Z-Leprfa/IzmDmcr Rats, a New Animal Model of Metabolic Syndrome
- Highly Sensitive Measurement of P-Glycoprotein-Mediated Transport Activity in Caco-2 Cells
- Effect of Vanadate on ATP-Induced Increase in Intracellular Calcium Ion Levels in Human Umbilical Vein Endothelial Cells
- Effects of ATP on the Intracellular Calcium Level in the Osteoblastic TBR31-2 Cell Line(Biochemistry)
- Studies on Anti-inflammatory Agents. VI. Synthesis and Pharmacological Properties of 2,3-Diarylthiophenes
- Studies on Anti-inflammatory Agents. V. Synthesis and Pharmacological Properties of 3-(Difluoromethyl)-1-(4-methoxyphenyl)-5-[4-(methylsulfinyl)phenyl]pyrazole and Related Compounds
- Studies on Anti-inflammatory Agents. IV. Synthesis and Pharmacological Properties of 1,5-Diarylpyrazoles and Related Derivatives
- Synthesis and Evaluation of Novel Pyrimido-Acridone, -Phenoxadine, and -Carbazole as Topoisomerase II Inhibitors
- A novel carbazole topoisomerase II poison, ER-37328 : potent tumoricidal activity against human solid tumors in vitro and in vivo
- Oxidants in the Gas Phase of Cigarette Smoke Pass Through the Lung Alveolar Wall and Raise Systemic Oxidative Stress
- Melatonin Inhibits the Central Sympatho-adrenomedullary Outflow in Rats
- EFFECT OF SHAKUYAKU-KANZOH-TOH, A PRESCRIPTION COMPOSED OF SHAKUYAKU (PAEONIAE RADIX) AND KANZOH (GLYCYRRHIZAE RADIX) ON GUINEA PIG ILEUM
- Microfluidic Polymer Chip with an Embedded Ion-Selective Electrode Detector for Nitrate-Ion Assay in Environmental Samples
- Dietary Corosolic Acid Ameliorates Obesity and Hepatic Steatosis in KK-Ay Mice(Pharmacognosy)
- Activation of Inwardly Rectifying K^+ Channel in OK Proximal Tubule Cells Involves cGMP-Dependent Phosphorylation Process
- Involvement of Inducible Nitric Oxide Synthase in Blood Flow Decrease in Vein Induced by Hen-Egg White Lysozyme(Miscellaneous)
- Development of an in Vivo Bioassay Method for Allergy-Preventive Substances Using Hen-Egg White Lysozyme (HEL)-Induced Blood Flow Decrease(Miscellaneous)
- Ginkgo biloba Extract markedly Induces Pentoxyresorufin O-Dealkylase Activity in Rats
- Amelioration of rewarming ischemic injury of the pancreas graft during vascular anastomosis by increasing tissue ATP contents during preservation by the two-layer cold storage method.
- Endothelin ET_A- and ET_B-Receptor-Mediated Inhibition of Noradrenaline Release From Isolated Rat Stomach
- Modulation of the Ca^-Activated Large Conductance K^+ Channel by Intracellular pH in Human Renal Proximal Tubule Cells
- Effect of Additives on Dissolution and Swelling of Soybean Lecithin Microcapsules Prepared Using the Wurster Process
- Phase Separation in Microcapsule Membranes Composed of Soybean Lecithin, Cholesterol, Stearic Acid and Polyvinylpyrrolidone
- Regulation of Inwardly Rectifying K^+ Channel in Cultured Opossum Proximal Tubule Cells by Protein Phosphatases 1 and 2A
- Isolation and Structure of Four New Ceramides from the Starfish Luidia maculata
- Isolation and Structure Determination of Six Glucocerebrosides from the Starfish Luidia maculata
- Changes of Contractile Properties of Extensor Digitorum Longus in Response to Creatine-Analogue Administration and/or Hindlimb Suspension in Rats
- Effects of Chronic Iron Deficiency Anemia on Brain Metabolism
- Source of ATP, ADP, AMP and Adenosine Released from Isolated Rat Caudal Artery Exposed to Noradrenaline
- POSSIBILITIES FOR ADENOSINE MODULATION OF PERISTALTIC REFLEX IN GUINEA PIG ISOLATED ILEUM
- PHYSIOLOGICAL IMPLICATION OF THE L-ARGININE-NITRIC OXIDE PATHWAY IN CIRCULATION
- Role of K^+ Channels in M_2 Muscarinic Receptor-Mediated Inhibition of Noradrenaline Release From the Rat Stomach
- Product Analyses of Ozone Mediated Nitration of Benzimidazole Derivatives with Nitrogen Dioxide : Formation of 1-Nitrobenzimidazoles and Conversion to Benzotriazoles
- Participation of Endogenous Noradrenaline in the Relaese of ATP by High Potassium in the Rat Caudal Artery
- Nicotinamide Derivatives as a New Class of Gastric (H^+/K^+)-ATPase Inhibitors. III. Synthesis and Gastric Antisecretory Activity of 2-[(2- and 4-Aminobenzyl, and α-methylbenzyl)sulfinyl]-N-(4-pyridinyl)-3-pyridinecarboxamides
- Nicotinamide Derivatives as a New Class of Gastric (H^+/k^+)-ATPase Inhibitors. II. Synthesis and Structure-Activity Relationships of 2-[(2,4-Dimethoxybenzyl)sulfinyl]-N-(4-pyridinyl)pyridine-3-carboxamides
- THE INFLUENCE OF EXTRACELLULAR Ca2+ CONCENTRATION ON THE INHIBITORY EFFECT OF ADENOSINE IN GUINEA-PIG ILEAL LONGITUDINAL MUSCLES
- Involvement of Endogenous Nitric Oxide in the Regulation of K^+ Channel Activity in Cultured Human Proximal Tubule Cells
- Effect of Bone Morphogenetic Protein-2 (BMP-2) or Troglitazone, as an Inducer of Osteogenic Cells or Adipocytes, on Differentiation of a Bone Marrow Mesenchymal Progenitor Cell Line Established from Temperature-Sensitive (ts) Simian Virus (SV) 40 T-Antige
- EXPERIMENTAL ATHEROSCLEROSIS IN RATS FED A VITAMIN D, CHOLESTEROL-RICH DIET
- Toxicologic Investigation of Dimethylacrylamide in Mice
- FUNDAMENTAL STUDIES OF ANTHELMINTICS (XXII). ELECTROPHYSIOLOGICAL STUDIES OF 1-[2-(DODECYLOXY) ETHYL]PYRROLIDINE HYDROCHLORIDE (DEP) ON ASCARIS MUSCLE CELLS
- FUNDAMENTAL STUDIES ON PHYSIOLOGICAL AND PHARMACOLOGICAL ACTIONS OF L-ASCORBATE 2-SULFATE. VI. EFFECTS OF L-ASCORBATE 2-SULFATE ON LIPID METABOLISM IN GUINEA PIGS
- FUNDAMENTAL STUDIES ON PHYSIOLOGICAL AND PHARMACOLOGICAL ACTIONS OF L-ASCORBATE 2-SULFATE. V. ON THE HYPOLIPIDEMIC AND ANTIATHEROSCLEROTIC EFFECTS OF L-ASCORBATE 2-SULFATE IN RABBITS
- An ATP-Regulated and pH-Sensitive Inwardly Rectifying K^+ Channel in Cultured Human Proximal Tubule Cells
- Properties of a Ca^-Activated Large Conductance K^+ Channel with ATP Sensitivity in Human Renal Proximal Tubule Cells
- Preventive effects of the extract of kinka-cha, a folk tea, on a rat model of metabolic syndrome
- Effects of Functional Food Constituents on P-glycoprotein Activity in Caco-2 Cells Determined by a New Method Using Confocal Laser Scanning Microscopy
- Effects of Short-term Ginkgo Biloba Extract Feeding on Hypotensive Action of Nicardipine in Rats
- Effects of cytokines on potassium channels in renal tubular epithelia
- Effects of ATP on the Intracellular Calcium Level in the Osteoblastic TBR31-2 Cell Line
- Reaction Mechanism and Improved Performance of Solution-Based Electrochemiluminescence Cell Driven by Alternating Current
- Advantage of Immobilization of Phthalate Derivatives on Indium Tin Oxide Electrode over TiO
- Effects of Cholesterol Loading on Autoimmune MRL-lpr/lpr Mice. Susceptibility to Hypercholesterolemia and Aortic Cholesterol Deposition.
- Pharmacological Analysis of Receptors Involved in the Late, Tachykininergic Contractile Response to Electrical Transmural Stimulation in Isolated Rabbit Iris Sphincter Muscle.
- Possible Participation of ATP in Changes of Blood Pressure in SHR and Old Rats
- Changes of platelet functions due to spontaneous hypertension: Reduced responses to Ionophore A23187 in SHRSP platelets
- Hyperlipidemic effects of adriamycin in rats.
- Suppression of adjuvant arthritis in rats by cholesterol.
- Abnormal lipid metabolism in adjuvant arthritic rats.
- Enhancing activity of anthranilic acid on adjuvant arthritis in rats and antibody formation in mice.
- Cholesterol reduces and corticosteroids enhance the toxicity of vitamin D in rats.
- Changes of platelet functions due to spontaneous hypertention: Effects of OP/CPK and/or ASA on platelet aggregation in SHRSP and WKY
- Hypertensive Effects of Nitroarginine:Comparison between WKY and SHRSP
- P2Y Receptor-Mediated Ca2+ Signaling Increases Human Vascular Endothelial Cell Permeability
- Changes in Platelet Functions due to Hypertension in The Rat VI. Comparison of Experimental Hypertension with Spontaneous Hypertension
- A Uniform Alteration in Serum Lipid Metabolism Occurring during Inflammation in Mice.
- Effects of adenosine on contractile response of circular muscle in electrically stimulated guinea-pig ileum.
- Lipid deposition in the aorta of adjuvant arthritic rats with hypercholesterolemia.
- Cholesterol metabolism in serum and aorta of inbred mice fed a high-cholesterol diet.
- Impairment of Endothelium-Dependent Relaxation in Aorta from Rats with Arteriosclerosis Induced by Excess Vitamin D and a High-Cholesterol Diet.
- Altered Vasoconstrictor Responsiveness in Vitamin D-Induced Arteriosclerotic Rat Aortas.
- Atherosclerosis mouse model induced by a high-cholesterol diet supplemented with .BETA.-aminopropionitrile: Effects of various anti-atherosclerotic agents on the biochemical parameters.
- Enthalpies of Hydrogen Bond Formation between Diphenylamines and Dimethyl Sulfoxide
- Determination of the Effects of Green Tea Extract and Fruit Extracts on P-glycoprotein Activity in Caco-2 Cells by Using a New Method Involving Confocal Laser Scanning Microscopy
- Effect of amide bond in gate dielectric polymers on memory performance of organic field-effect transistors