Chronic administration of olmesartan attenuates the exaggerated pressor response to glutamate in the rostral ventrolateral medulla of SHR

Yingzi Lin, Kiyoshi Matsumura, Shuntaro Kagiyama, Masayo Fukuhara, Koji Fujii, Mitsuo Iida

研究成果: ジャーナルへの寄稿学術誌査読

22 被引用数 (Scopus)

抄録

It has been shown that the pressor responses to microinjection of l-glutamate in the rostral ventrolateral medulla (RVLM) are augmented in spontaneously hypertensive rats (SHR), and that these augmented responses are not altered by chronic conventional antihypertensive treatment. The aim of the present study was to determine the effect of chronic oral treatment with a new angiotensin II type 1 (AT1) receptor antagonist, RNH-6270 (the active form of olmesartan medoxomil), on cardiovascular responses to excitatory amino acids in the RVLM of SHR. SHR (12 weeks old) were treated with RNH-6270 (30 mg/kg/day) or vehicle for 4 weeks. At 16 weeks of age, l-glutamate (2 nmol), N-methyl-d-aspartate (NMDA; an ionotropic glutamate receptor agonist (20 pmol)), or (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid ((1S,3R)-ACPD; a metabotropic glutamate receptor agonist (1 nmol)) was microinjected into the RVLM of rats. The pressor responses to microinjection of l-glutamate or NMDA in the RNH-6270-treated SHR (+28.3 ± 1.0 and +48.3 ± 2.5 mm Hg, respectively) were significantly smaller than those in untreated SHR (+45.7 ± 2.2 and +69.4 ± 7.0 mm Hg, respectively, P < 0.05 each); however, they were still greater than those in the Wistar-Kyoto rats (+21.7 ± 1.0 and +28.6 ± 3.3 mm Hg, respectively, P < 0.05 each). In contrast, the augmented pressor responses to microinjection of (1S,3R)-ACPD in SHR were not affected by the RNH-6270 treatment. These results demonstrated that chronic oral treatment with RNH-6270, an AT1 receptor antagonist, partly normalizes the pressor responses to l-glutamate or NMDA, but not (1S,3R)-ACPD, in the RVLM of SHR, suggesting that endogenous angiotensin II may be involved in the exaggerated pressor response to l-glutamate, probably through its ionotropic glutamate receptors.

本文言語英語
ページ(範囲)161-166
ページ数6
ジャーナルBrain Research
1058
1-2
DOI
出版ステータス出版済み - 10月 5 2005

!!!All Science Journal Classification (ASJC) codes

  • 神経科学一般
  • 分子生物学
  • 臨床神経学
  • 発生生物学

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