Chronic administration of olmesartan attenuates the exaggerated pressor response to glutamate in the rostral ventrolateral medulla of SHR
Chronic administration of olmesartan attenuates the exaggerated pressor response to glutamate in the rostral ventrolateral medulla of SHR
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DOI：
10.1016/j.brainres.2005.07.070
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发表时间：
2005-10-05
期刊：
影响因子：
2.9
通讯作者：
Iida, M
中科院分区：
文献类型：
--
作者：
Lin, YZ;Matsumura, K;Iida, M
研究表明，自发性高血压大鼠（SHR）在吻侧腹外侧髓质（RVLM）微注射l -谷氨酸后的升压反应增强，并且这些增强的反应不受慢性常规降压治疗的影响。本研究的目的是确定慢性口服一种新的血管紧张素11 1型（AT(1)）受体拮抗剂RNH-6270（奥美沙坦美多索米的活性形式）对SHR RVLM中兴奋性氨基酸的心血管反应的影响。12周龄的SHR用RNH-6270 （30 mg/kg/天）或载药治疗4周。16周龄时，l-谷氨酸（2 nmol）， n -甲基-d -天冬氨酸（NMDA；一种离子型谷氨酸受体激动剂（20 pmol）），或(1S,3R)-1-氨基环戊烷-1,3-二羧酸((1S,3R)-ACPD；将代谢性谷氨酸受体激动剂（1 nmol）微注射大鼠RVLM。rnh -6270处理的SHR组中l -谷氨酸和NMDA微注射的升压反应（分别为+28.3 +/- 1.0和+483 +/- 2.5 mm Hg）显著小于未处理的SHR组（分别为+45.7 +/- 2.2和+69.4 +/- 7.0 mm Hg, P < 0.05）；但仍高于Wistar-Kyoto大鼠（+21.7 +/- 1.0和+28.6 +/- 3.3 min Hg, P < 0.05）。相比之下，RNH-6270处理不影响SHR中显微注射(1S,3R)-ACPD增强的升压反应。这些结果表明，长期口服AT受体拮抗剂RNH-6270可部分恢复SHR RVLM中对l -谷氨酸或NMDA的升压反应，但不能恢复(1S,3R)-ACPD的升压反应，提示内源性血管紧张素11可能通过其嗜离子性谷氨酸受体参与了对l -谷氨酸的过度升压反应。(c) 2005 Elsevier b.v.版权所有
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 anti hypertensive treatment. The aim of the present study was to determine the effect of chronic oral treatment with a new angiotensin 11 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 (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 +483 +/- 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 min 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 AT, 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 11 may be involved in the exaggerated pressor response to L-glutamate, probably through its ionotropic glutamate receptors. (c) 2005 Elsevier B.V All rights reserved.