This Article Full Text Full Text (PDF) All Versions of this Article: 44/4/478    most recent 01.HYP.0000143120.24612.68v1 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 Ito, K. Articles by Sunagawa, K. Search for Related Content PubMed PubMed Citation Articles by Ito, K. Articles by Sunagawa, K. Pubmed/NCBI databases Substance via MeSH Related Collections Animal models of human disease Hypertension - basic studies Autonomic, reflex, and neurohumoral control of circulation

(Hypertension. 2004;44:478.)
© 2004 American Heart Association, Inc.

Scientific Contributions

Inhibition of Rho-Kinase in the Brainstem Augments Baroreflex Control of Heart Rate in Rats

Koji Ito; Yoshitaka Hirooka; Yoji Sagara; Yoshikuni Kimura; Kozo Kaibuchi; Hiroaki Shimokawa; Akira Takeshita; Kenji Sunagawa

From the Department of Cardiovascular Medicine (K.I., Y.H., Y.S., Y.K., H.S., A.T., K.S.), Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan; Department of Cell Pharmacology (K.K.), Nagoya University Graduate School of Medicine, Nagoya, Japan.

Correspondence to Dr Yoshitaka Hirooka, 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

The Rho/Rho-kinase pathway in the nucleus tractus solitarii (NTS) of the brain stem contributes to blood pressure regulation. Activation of this pathway might be involved in the central nervous system mechanisms of hypertension. The aim of the present study was to determine whether baroreflex control of heart rate is altered by inhibition of Rho-kinase in the NTS. Adenovirus vectors encoding dominant-negative Rho-kinase or ß-galactosidase were transfected into the nucleus tractus solitarii of Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). Baroreflex control of heart rate was examined by changing arterial pressure with an intravenous infusion of phenylephrine or sodium nitroprusside. The maximum gain of baroreflex control of heart rate was attenuated in SHR compared with WKY before the gene transfer. Transfection of adenovirus vectors encoding dominant-negative Rho-kinase significantly augmented the maximum gain in both WKY and SHR. The extent of this augmentation, however, was greater in SHR than in WKY. After treatment with metoprolol, the maximum gain was significantly decreased in rats transfected with adenovirus vectors encoding dominant-negative Rho-kinase, but not in nontransfected rats. In contrast, after treatment with atropine, the maximum gain was greater in rats transfected with adenovirus vectors encoding dominant-negative Rho-kinase compared with nontransfected rats, although it was decreased in both groups. These results suggest that inhibition of Rho-kinase in the NTS augments baroreflex control of heart rate, in both WKY and SHR, probably because of a cardiac sympathoinhibitory effect.

Key Words: blood pressure • heart rate • rho • hypertension • brain

This article has been cited by other articles:

				K. Ito, Y. Hirooka, and K. Sunagawa Acquisition of Brain Na Sensitivity Contributes to Salt-Induced Sympathoexcitation and Cardiac Dysfunction in Mice With Pressure Overload Circ. Res., April 24, 2009; 104(8): 1004 - 1011. [Abstract] [Full Text] [PDF]

				K. Ito, Y. Hirooka, Y. Kimura, Y. Sagara, and K. Sunagawa Ovariectomy Augments Hypertension Through Rho-Kinase Activation in the Brain Stem in Female Spontaneously Hypertensive Rats Hypertension, October 1, 2006; 48(4): 651 - 657. [Abstract] [Full Text] [PDF]

				T. M. Seasholtz, J. Wessel, F. Rao, B. K. Rana, S. Khandrika, B. P. Kennedy, E. O. Lillie, M. G. Ziegler, D. W. Smith, N. J. Schork, et al. Rho Kinase Polymorphism Influences Blood Pressure and Systemic Vascular Resistance in Human Twins: Role of Heredity Hypertension, May 1, 2006; 47(5): 937 - 947. [Abstract] [Full Text] [PDF]

				H. Shimokawa and A. Takeshita Rho-Kinase Is an Important Therapeutic Target in Cardiovascular Medicine Arterioscler Thromb Vasc Biol, September 1, 2005; 25(9): 1767 - 1775. [Abstract] [Full Text] [PDF]

				K. Ito, Y. Hirooka, N. Hori, Y. Kimura, Y. Sagara, H. Shimokawa, A. Takeshita, and K. Sunagawa Inhibition of Rho-Kinase in the Nucleus Tractus Solitarius Enhances Glutamate Sensitivity in Rats Hypertension, August 1, 2005; 46(2): 360 - 365. [Abstract] [Full Text] [PDF]