Effect of overproduction of nitric oxide in the brain stem on the cardiovascular response in conscious rats.
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 sympathetic 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 gamma-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.
Hirooka
Yoshitaka
Y
Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan. hyoshi@cardiol.med.kyushu-u.ac.jp
Kishi
Takuya
T
Sakai
Koji
K
Shimokawa
Hiroaki
H
Takeshita
Akira
A
D000818:Animals; D001933:Brain Stem / Q000378:metabolism*; D002319:Cardiovascular System / Q000378:metabolism*; D003243:Consciousness / Q000502:physiology*; D006801:Humans; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D052250:Nitric Oxide Synthase Type III
D009569:Nitric Oxide; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III