title: Peroxynitrite is Involved in the dysfunction of vasorelaxation in SHR/NDmcr-cp rats, spontaneously hypertensive obese rats.
abstract: SHR/NDmcr-cp (SHR-cp) rats display typical symptoms and features of the metabolic syndrome. We previously reported that endothelium-dependent relaxation decreases in the thoracic aortas of SHR-cp rats, despite increased nitric oxide (NO) production from the endothelium. In the present study, to search for the reasons for this contradiction, we investigated whether vascular abnormality could be reduced by treatment of SHR-cp rats with antihypertensive drugs; a calcium channel blocker (amlodipine), an alpha 2 and imidazoline receptor agonist (moxonidine), and an angiotensin II type 1 (AT1) receptor antagonist (telmisartan). Telmisartan but not amlodipine and moxonidine ameliorated the impairment of relaxation in response to acetylcholine and the increased protein expression of endothelium NO synthase in thoracic aortas. All three drugs significantly lowered the blood pressure. Telmisartan decreased the serum levels of lipid peroxide and 8-hydroxy-2'-deoxyguanosine, oxidative stress markers, and also the aortic levels of the protein expression of gp91, a component of NADPH oxidase, and 3-nitrotyrosine, a biomarker of peroxynitrite. These findings suggest that NADPH oxidase-derived superoxide, probably produced due to stimulation of AT1 receptors, reacts with NO to form peroxynitrite, and consequently decreases active NO, leading to attenuation of endothelium-dependent relaxation. Angiotensin receptor antagonists may be effective for preventing endothelial dysfunction in metabolic syndrome.
authors: Department of Pharmacology, School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women's University, Nishinomiya, Japan. skagota@mukogawa-u.ac.jp
authors: Satomi
authors: S
authors: Kagota
authors: Yukari
authors: Y
authors: Tada
authors: Yoko
authors: Y
authors: Kubota
authors: Namie
authors: N
authors: Nejime
authors: Yu
authors: Y
authors: Yamaguchi
authors: Kazuki
authors: K
authors: Nakamura
authors: Masaru
authors: M
authors: Kunitomo
authors: Kazumasa
authors: K
authors: Shinozuka
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D017311:Amlodipine / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D015153:Blotting, Western; D002784:Cholesterol / Q000097:blood; D006152:Cyclic GMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000378:metabolism / Q000503:physiopathology*; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D007328:Insulin / Q000097:blood; D008297:Male; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology; D009765:Obesity / Q000378:metabolism / Q000503:physiopathology*; D030421:Peroxynitrous Acid / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR; D011922:Rats, Mutant Strains; D014280:Triglycerides / Q000097:blood; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
chemical_list: D001786:Blood Glucose; D007093:Imidazoles; D007328:Insulin; D014280:Triglycerides; D030421:Peroxynitrous Acid; D009599:Nitroprusside; D017311:Amlodipine; D002784:Cholesterol; C043482:moxonidine; D052250:Nitric Oxide Synthase Type III; D006152:Cyclic GMP; D000109:Acetylcholine