Role of the Central Nervous System in the Development of Hypertension Produced by Chronic Nitric Oxide Blockade in Rats.

• NAKATA Tetsuo

  Clinical Pharmacology, Kyoto Pharmaceutical University

• TAKEDA Kazuo

  Second Department of Medicine, Kyoto Prefectural University of Medicine

• HARADA Sanae

  Second Department of Medicine, Kyoto Prefectural University of Medicine

• OGUNI Atsuhiko

  Second Department of Medicine, Kyoto Prefectural University of Medicine

• HATTA Tsuguru

  Second Department of Medicine, Kyoto Prefectural University of Medicine

• KAWA Tetsuyoshi

  Second Department of Medicine, Kyoto Prefectural University of Medicine

• ITOH Hiroshi

  Second Department of Medicine, Kyoto Prefectural University of Medicine

• SASAKI Susumu

  Second Department of Medicine, Kyoto Prefectural University of Medicine

• NAKAGAWA Masao

  Second Department of Medicine, Kyoto Prefectural University of Medicine

抄録

We examined the role of the central nervous system, and particularly the renin-angiotensin (RA) system, in the development of hypertension produced by chronic inhibition of NO synthesis. In experiment 1, Wistar rats drank either nitro-L-arginine-methyl ester (L-NAME) or tap water. Before L-NAME treatment rats were divided into 6 groups. Four of them were administered either losartan or artificial cerebroventricular fluid (a-CSF) intracerebroventricularly (i.c.v.) for 1 week using an osmotic mini pump. The other two groups were administered the same amount of losartan intravenously (i.v.). In experiment 2, cardiovascular responses to acute i.c.v. losartan and muscimol, a GABA_A agonist, were examined in conscious L-NAME-treated rats. Finally, in experiment 3, effects of ablation of the AV3V (anteroventral third ventricle) area, known to be one of the centers of cardiovascular control, were tested in the development of L-NAME hypertension. The development of hypertension by L-NAME treatment was attenuated with chronic i.c.v. losartan in a dose-dependent manner, while i.v. losartan had no effect. One week after cessation of i.c.v. losartan, blood pressure was elevated to the same level as in a-CSF-infused, L-NAME-treated rats. Acute i.c.v. losartan produced no cardiovascular changes in either L-NAME-treated or control rats. On the other hand, although i.c.v. muscimol elicited depressor effects in both groups, these responses were significantly larger in L-NAME-treated rats. Cardiovascular responses to i.v. hexamethonium were similar in both groups. The existence of prior lesions in the AV3V area significantly attenuated the development of L-NAME-induced hypertension. These results indicate that the central RA system plays an important role in the development of hypertension produced by chronic inhibition of NO synthase. Moreover, disorder of the central GABA system, rather than that of the RA system, might be important in the maintenance of hypertension in this model. (Hypertens Res 2001; 24: 39-45)

収録刊行物

• Hypertension Research

  Hypertension Research 24 (1), 39-45, 2001

  日本高血圧学会

キーワード

• nitric oxide
• losartan
• central nervous system
• GABA
• AV3V

詳細情報

• CRID: 1390282679695537152
• NII論文ID: 10008741951
• NII論文ID: 30002004556
• NII書誌ID: AA10847079
• DOI: 10.1291/hypres.24.39
• COI: 1:CAS:528:DC%2BD3MXhtl2iurw%3D
• ISSN: 13484214
• ISSN: 09169636
• PubMed: 11213029
• Web Site: https://search.jamas.or.jp/link/ui/2001148981
• 本文言語コード: en
• データソース種別:
  • JaLC
  • Crossref
  • PubMed
  • CiNii Articles
• 抄録ライセンスフラグ: 使用不可