Effects of Angiotensin Ⅱ AT₁-Receptor Blockade on High Fat Diet-Induced Vascular Oxidative Stress and Endothelial Dysfunction in Dahl Salt-Sensitive Rats

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  • Kosaka Shinji
    Department of Pharmacy, Kagawa University Hospital, Japan Department of Pharmacology, Kagawa University Medical School, Japan
  • Pelisch Nicolas
    Department of Pharmacology, Kagawa University Medical School, Japan
  • Rahman Matlubur
    Department of Pharmacology, Kagawa University Medical School, Japan
  • Nakano Daisuke
    Department of Pharmacology, Kagawa University Medical School, Japan
  • Hitomi Hirofumi
    Department of Pharmacology, Kagawa University Medical School, Japan
  • Kobori Hiroyuki
    Department of Pharmacology, Kagawa University Medical School, Japan
  • Fukuoka Noriyasu
    Department of Pharmacy, Kagawa University Hospital, Japan
  • Kobara Hideki
    Department of Gastroenterology, Kagawa University Medical School, Japan
  • Mori Hirohito
    Department of Gastroenterology, Kagawa University Medical School, Japan
  • Masaki Tsutomu
    Department of Gastroenterology, Kagawa University Medical School, Japan
  • Cervenka Ludek
    Department for Experimental Medicine, Institute for Clinical and Experimental Medicine, Czech Republic
  • Matsumura Yasuo
    Laboratory of Pathological and Molecular Pharmacology, Osaka University of Pharmaceutical Sciences, Japan
  • Houchi Hitoshi
    Department of Pharmacy, Kagawa University Hospital, Japan
  • Nishiyama Akira
    Department of Pharmacology, Kagawa University Medical School, Japan

書誌事項

タイトル別名
  • Effects of Angiotensin II AT<sub>1</sub>–Receptor Blockade on High Fat Diet–Induced Vascular Oxidative Stress and Endothelial Dysfunction in Dahl Salt-Sensitive Rats
  • Effects of Angiotensin II AT1^|^ndash;Receptor Blockade on High Fat Diet^|^ndash;Induced Vascular Oxidative Stress and Endothelial Dysfunction in Dahl Salt-Sensitive Rats

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抄録

We examined the effects of angiotensin II AT1–receptor blockade with olmesartan on high fat (HF) diet–induced vascular oxidative stress and endothelial dysfunction in normal salt (NS) diet–fed Dahl salt-sensitive (DSS) rats. Treatment with NS + HF diet (32% crude fat, 0.3% NaCl) for 20 weeks significantly increased blood pressure in DSS rats. NS + HF diet–fed DSS rats also showed higher plasma levels of thiobarbituric acid–reactive substances, aortic superoxide production, and mRNA levels of p22phox and gp91phox in aortic tissues than NS diet–fed DSS rats. Furthermore, acetylcholine-induced vasorelaxation of aorta from NS + HF diet–fed DSS rats was significantly reduced. In NS + HF diet–fed DSS rats, treatment with olmesartan medoxomil (10 mg/kg per day, p.o.) and hydralazine (25 mg/kg per day, p.o.) similarly decreased blood pressure. However, in these animals, only olmesartan normalized plasma levels of thiobarbituric acid–reactive substances, vascular superoxide in aortic tissues, and acetylcholine-induced vasorelaxation. These data indicate that HF diet–induced hypertension is associated with vascular oxidative stress and endothelial dysfunction in NS diet–treated DSS rats. Inhibition of angiotensin II AT1 receptors may elicit beneficial effects on HF-induced hypertension and vascular injury in subjects that have genetically enhanced sodium-sensitive blood pressure.

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