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(Hypertension. 2001;38:896.)
© 2001 American Heart Association, Inc.

Scientific Contributions

Overexpression of eNOS in the RVLM Causes Hypotension and Bradycardia Via GABA Release

Takuya Kishi; Yoshitaka Hirooka; Koji Sakai; Hideaki Shigematsu; Hiroaki Shimokawa; Akira Takeshita

From the Department of Cardiovascular Medicine, Cardiovascular Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Correspondence to Yoshitaka Hirooka, MD, PhD, Department of Cardiovascular Medicine, Cardiovascular Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. E-mail hyoshi{at}cardiol.med.kyushu-u.ac.jp

Abstract—— In this study, we examine the role of NO located in the rostral ventrolateral medulla (RVLM) in the control of blood pressure and the activity of the sympathetic nervous system. To determine the effect of an increase in NO production in the RVLM on blood pressure in conscious rats, adenovirus vectors encoding either endothelial NO synthase (AdeNOS) or ß-galactosidase (Adßgal) were transfected into the bilateral RVLM. The local expression of endothelial NO synthase (eNOS) protein in the RVLM was confirmed by immunohistochemical staining for the eNOS protein and by Western blot analysis. Mean arterial blood pressure (MAP) and heart rate, which were monitored using a radio-telemetry system, were significantly decreased in the AdeNOS-treated group from day 5 to day 10 after the gene transfer. Urinary norepinephrine excretion was decreased on day 7 after the gene transfer in the AdeNOS-treated group. Microinjection of either N^G-monomethyl-L-arginine (L-NMMA) or bicuculine, a -amino butyric acid (GABA) receptor antagonist, into the RVLM at day 7 after the gene transfer increased MAP to significantly greater levels in the AdeNOS-treated group. However, microinjection of kynurenic acid into the RVLM on day 7 after the gene transfer did not alter MAP levels in either group. GABA and glutamate levels in the RVLM, when measured by in vivo microdialysis, were significantly increased in the AdeNOS-treated group. These results suggest that the increase in NO production caused by the overexpression of eNOS in the bilateral RVLM decreases blood pressure, heart rate, and sympathetic nerve activity in conscious rats. Furthermore, these responses may be mediated by an increased release of GABA in the RVLM.

Key Words: genes • nitric oxide • cardiovascular regulation • brain • sympathetic nervous system

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