Effect of overproduction of nitric oxide in the brain stem on the cardiovascular response in conscious rats

Yoshitaka Hirooka, Takuya Kishi, Koji Sakai, Hiroaki Shimokawa, Akira Takeshita

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Abstract

To examine the role of nitric oxide in the brain stem on cardiovascular response in vivo, we have developed and applied a technique of endothelial nitric oxide synthase gene transfer into the nucleus tractus solitarii or the rostral ventrolateral medulla of rats in vivo. The blood pressure and heart rate were monitored using a radiotelemetry system in the conscious state. As a marker of sym syrnpathetic nerve activity, we measured 24-h urinary norepinephrine excretion. We found that overexpression of endothelial nitric oxide synthase in the nucleus tractus solitarii as well as in the rostral ventrolateral medulla causes hypotension and bradycardia via a decrease in sympathetic nerve activity. Furthermore, in the case of the local increases in nitric oxide in the rostral ventrolateral medulla, we suggest that this effect is mediated by an increase in γ-aminobutyric acid. Moreover, in the stroke-prone spontaneously hypertensive rat, the increase in nitric oxide production evoked by the overexpression of endothelial nitric oxide synthase in the rostral ventrolateral medulla caused greater depressor and sympatho-inhibitory responses than in normotensive Wistar-Kyoto rats, suggesting that an abnormality of the L-arginine-nitric oxide pathway may be involved in the central mechanisms of hypertension in this model.

Original languageEnglish
Pages (from-to)S119-S126
JournalJournal of Cardiovascular Pharmacology
Volume41
Issue numberSUPPL. 1
Publication statusPublished - Jan 1 2003

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All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

Cite this

Hirooka, Y., Kishi, T., Sakai, K., Shimokawa, H., & Takeshita, A. (2003). Effect of overproduction of nitric oxide in the brain stem on the cardiovascular response in conscious rats. Journal of Cardiovascular Pharmacology, 41(SUPPL. 1), S119-S126.