This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kishi, T. Articles by Takeshita, A. Search for Related Content PubMed PubMed Citation Articles by Kishi, T. Articles by Takeshita, A. Related Collections Animal models of human disease Other hypertension Gene expression Physiological and pathological control of gene expression Autonomic, reflex, and neurohumoral control of circulation

(Hypertension. 2002;39:264.)
© 2002 American Heart Association, Inc.

Scientific Contributions

Cardiovascular Effects of Overexpression of Endothelial Nitric Oxide Synthase in the Rostral Ventrolateral Medulla in Stroke-Prone Spontaneously Hypertensive Rats

Takuya Kishi; Yoshitaka Hirooka; Koji Ito; Koji Sakai; Hiroaki Shimokawa; Akira Takeshita

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

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

We have previously demonstrated that the overexpression of endothelial NO synthase (eNOS) in the rostral ventrolateral medulla (RVLM) decreases blood pressure, heart rate, and sympathetic nerve activity via an increase in -amino butyric acid release in normotensive Wistar-Kyoto rats (WKY). Stroke-prone spontaneously hypertensive rats (SHRSP) appear to have reductions of NO production and GABA release in the RVLM. The aim of this study was to determine whether the effects of the increase in NO production in the RVLM in SHRSP are different from those in WKY. We transfected adenovirus vectors encoding either eNOS (AdeNOS) or ß-galactosidase (Adßgal) into the RVLM of both strains. In the AdeNOS-treated group, mean arterial blood pressure and heart rate in the conscious state were significantly decreased at day 7 after the gene transfer in both strains. The decreases in mean arterial blood pressure and heart rate were significantly greater in SHRSP than in WKY. Urinary norepinephrine excretion was also decreased to a greater degree in SHRSP than in WKY after the gene transfer. The pressor response evoked by bicuculline into the RVLM of WKY was greater than that of SHRSP in the nontransfected group. However, in the AdeNOS-treated group, the pressor response did not differ between SHRSP and WKY after the gene transfer. These results indicate that the increase in NO production evoked by the overexpression of eNOS in the RVLM causes greater depressor and sympathoinhibitory responses in SHRSP than in WKY by improving an inhibitory action of GABA on the RVLM neurons.

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

This article has been cited by other articles:

				L. Gao, W. Wang, and I. H. Zucker Simvastatin Inhibits Central Sympathetic Outflow in Heart Failure by a Nitric-Oxide Synthase Mechanism J. Pharmacol. Exp. Ther., July 1, 2008; 326(1): 278 - 285. [Abstract] [Full Text] [PDF]

				M. Nozoe, Y. Hirooka, Y. Koga, Y. Sagara, T. Kishi, J. F. Engelhardt, and K. Sunagawa Inhibition of Rac1-Derived Reactive Oxygen Species in Nucleus Tractus Solitarius Decreases Blood Pressure and Heart Rate in Stroke-Prone Spontaneously Hypertensive Rats Hypertension, July 1, 2007; 50(1): 62 - 68. [Abstract] [Full Text] [PDF]

				K. Sakai, Y. Hirooka, H. Shigematsu, T. Kishi, K. Ito, H. Shimokawa, A. Takeshita, and K. Sunagawa Overexpression of eNOS in brain stem reduces enhanced sympathetic drive in mice with myocardial infarction Am J Physiol Heart Circ Physiol, November 1, 2005; 289(5): H2159 - H2166. [Abstract] [Full Text] [PDF]

				T. B.J. Kuo and C. C.H. Yang Sleep-Related Changes in Cardiovascular Neural Regulation in Spontaneously Hypertensive Rats Circulation, August 9, 2005; 112(6): 849 - 854. [Abstract] [Full Text] [PDF]

				Y. Kimura, Y. Hirooka, Y. Sagara, K. Ito, T. Kishi, H. Shimokawa, A. Takeshita, and K. Sunagawa Overexpression of Inducible Nitric Oxide Synthase in Rostral Ventrolateral Medulla Causes Hypertension and Sympathoexcitation via an Increase in Oxidative Stress Circ. Res., February 4, 2005; 96(2): 252 - 260. [Abstract] [Full Text] [PDF]

				H.-N. Huang, P.-J. Lu, W.-C. Lo, C.-H. Lin, M. Hsiao, and C.-J. Tseng In Situ Akt Phosphorylation in the Nucleus Tractus Solitarii Is Involved in Central Control of Blood Pressure and Heart Rate Circulation, October 19, 2004; 110(16): 2476 - 2483. [Abstract] [Full Text] [PDF]

				T. Kishi, Y. Hirooka, Y. Kimura, K. Ito, H. Shimokawa, and A. Takeshita Increased Reactive Oxygen Species in Rostral Ventrolateral Medulla Contribute to Neural Mechanisms of Hypertension in Stroke-Prone Spontaneously Hypertensive Rats Circulation, May 18, 2004; 109(19): 2357 - 2362. [Abstract] [Full Text] [PDF]

				J. Y.H. Chan, L.-L. Wang, Y.-M. Chao, and S. H.H. Chan Downregulation of Basal iNOS at the Rostral Ventrolateral Medulla Is Innate in SHR Hypertension, March 1, 2003; 41(3): 563 - 570. [Abstract] [Full Text] [PDF]