Angiotensin in the nucleus tractus solitarii contributes to neurogenic hypertension caused by chronic nitric oxide synthase inhibition

Kenichi Eshima, Yoshitaka Hirooka, Hideaki Shigematsu, Isamu Matsuo, George Koike, Koji Sakai, Akira Takeshita

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60 Citations (Scopus)

Abstract

Activation of the sympathetic nervous system and renin-angiotensin system has been suggested to contribute to the hypertension caused by chronic nitric oxide synthase inhibition. The aim of the present study was to determine whether angiotensin within the nucleus tractus solitarii (NTS) plays a role in activation of the sympathetic nervous system in this model. Rats were treated with N(ω)-nitro-L-arginine methyl ester (L-NAME, 100 mg · kg-1 · d-1 in drinking water) for 2 weeks. Experiments were performed on anesthetized rats with denervated arterial and cardiopulmonary baroreceptors. Arterial pressure, heart rate, and renal sympathetic nerve activity (RSNA) were measured. Microinjection of an angiotensin II type 1 (AT1) receptor antagonist (CV11974) or an angiotensin II type 2 (AT2) receptor antagonist (PD123319) into the depressor region within the NTS (identified by prior injection of L-glutamate) Was performed Microinjection of CV11974, but not of PD 123319, produced greater decreases in arterial pressure, heart rate, and RSNA in L-NAME-treated rats than in control rats. The administration of hexamethonium resulted in a larger fall in arterial pressure in L-NAME-treated rats than in control rats. The ACE mRNA level in the brain stem was greater in L-NAME-treated rats than in control rats. These results suggest that increased sympathetic nerve activity plays a role in hypertension caused by chronic nitric oxide synthase inhibition and that activation of the renin-angiotensin system in the NTS is involved at least in part in this increased sympathetic nerve activity via AT1 receptors.

Original languageEnglish
Pages (from-to)259-263
Number of pages5
JournalHypertension
Volume36
Issue number2
DOIs
Publication statusPublished - 2000

All Science Journal Classification (ASJC) codes

  • Internal Medicine

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