title: Effects of angiotensin II AT₁-receptor blockade on high fat diet-induced vascular oxidative stress and endothelial dysfunction in Dahl salt-sensitive rats.
abstract: 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 p22(phox) and gp91(phox) 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.
authors: Department of Pharmacology, Kagawa University Medical School, Kagawa, Japan.
authors: Shinji
authors: S
authors: Kosaka
authors: Nicolas
authors: N
authors: Pelisch
authors: Matlubur
authors: M
authors: Rahman
authors: Daisuke
authors: D
authors: Nakano
authors: Hirofumi
authors: H
authors: Hitomi
authors: Hiroyuki
authors: H
authors: Kobori
authors: Noriyasu
authors: N
authors: Fukuoka
authors: Hideki
authors: H
authors: Kobara
authors: Hirohito
authors: H
authors: Mori
authors: Tsutomu
authors: T
authors: Masaki
authors: Ludek
authors: L
authors: Cervenka
authors: Yasuo
authors: Y
authors: Matsumura
authors: Hitoshi
authors: H
authors: Houchi
authors: Akira
authors: A
authors: Nishiyama
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D059305:Diet, High-Fat / Q000009:adverse effects*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D006830:Hydralazine / Q000494:pharmacology; D006973:Hypertension / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000096:biosynthesis / Q000378:metabolism; D000068557:Olmesartan Medoxomil; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D020303:Rats, Inbred Dahl; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism; D013777:Tetrazoles / Q000494:pharmacology; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D007093:Imidazoles; D008562:Membrane Glycoproteins; D044140:Receptor, Angiotensin, Type 1; D013777:Tetrazoles; D017392:Thiobarbituric Acid Reactive Substances; D013481:Superoxides; D006830:Hydralazine; D000068557:Olmesartan Medoxomil; C500593:Cybb protein, rat; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; C515768:Cyba protein, rat