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

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 (AT 1) 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 (1 S,3 R)-1-aminocyclopentane-1,3-dicarboxylic acid ((1 S,3 R)-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