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

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Author(s)

    • 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

Abstract

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<SUB>A</SUB> 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)

Journal

  • Hypertension Research

    Hypertension Research 24(1), 39-45, 2001-01-01

    The Japanese Society of Hypertension

References:  35

Cited by:  1

Codes

  • NII Article ID (NAID)
    10008741951
  • NII NACSIS-CAT ID (NCID)
    AA10847079
  • Text Lang
    ENG
  • Article Type
    Journal Article
  • ISSN
    09169636
  • Data Source
    CJP  CJPref  J-STAGE 
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