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

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Abstract

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.

Original languageEnglish
Pages (from-to)161-166
Number of pages6
JournalBrain Research
Volume1058
Issue number1-2
DOIs
Publication statusPublished - Oct 5 2005

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All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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