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ABNORMALITIES OF NITRIC OXIDE‐MEDIATED VASORELAXATION IN A RAT MODEL OF METABOLIC SYNDROME: INVOLVEMENT OF PEROXYNITRITE FORMATION
Author(s) -
Kagota Satomi,
Tada Yukari,
Yamaguchi Yu,
Kubota Yoko,
Nejime Namie,
Nakamura Kazuki,
Kunitomo Masaru,
Shinozuka Kazumasa
Publication year - 2007
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.2007.04765.x
Subject(s) - telmisartan , peroxynitrite , endocrinology , medicine , chemistry , nitric oxide , endothelial dysfunction , angiotensin ii , nitrotyrosine , asymmetric dimethylarginine , nitric oxide synthase , blood pressure , superoxide , arginine , biochemistry , amino acid , enzyme
SUMMARY1 We reported previously that nitric oxide (NO)‐mediated relaxation is impaired, despite an increase in NO production from the endothelium, in the thoracic aorta of SHR/NDmcr‐cp (SHR‐cp) rats, an animal model of the metabolic syndrome. In the present study, we investigated whether telmisartan, an angiotensin II receptor antagonist, can improve abnormal vasorelaxation responses. 2 Treatment with telmisartan (10 mg/kg per day, p.o.) for 8 weeks reduced elevated blood pressure in SHR‐cp rats, but did not affect the increased bodyweight, serum triglyceride and glucose levels. Telmisartan restored impaired acetylcholine‐induced relaxation. Both increased endothelial NO synthase protein expression in aortas and 3‐nitrotyrosine content, evidence of peroxynitrite formation, were significantly suppressed by telmisartan. Serum levels of thiobarbituric acid‐reactive substances, an index of oxidized lipids, were significantly decreased. 3 These results suggest that telmisartan can reduce the decline in NO bioavailability caused by peroxynitrite formation in the aortas of SHR‐cp rats. We propose that antagonism of angiotensin II action may be effective in preventing vascular endothelial dysfunction in metabolic syndrome.