Published online before print June 5, 2003, doi: 10.1161/01.RES.0000079941.59846.D4
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
© 2003 American Heart Association, Inc.
Integrative Physiology |
Rho/Rho-Kinase Pathway in Brain Stem Contributes to Blood Pressure Regulation via Sympathetic Nervous System
Possible Involvement in Neural Mechanisms of Hypertension
From the Department of Cardiovascular Medicine (K.I., Y.H., K.S., T.K., H.S., A.T.), Kyushu University Graduate School of Medical Sciences, Fukuoka, and the Department of Cell Pharmacology (K.K.), Nagoya University Graduate School of Medicine, Nagoya, Japan.
Correspondence to Yoshitaka Hirooka, MD, PhD, FAHA, 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
Recent studies have demonstrated that the Rho/Rho-kinase pathway plays an important role in various cellular functions, including actin cytoskeleton organization and vascular smooth muscle contraction. This pathway is also present in the central nervous system and is involved in the maintenance of dendritic spines and axon outgrowth and in the regulation of neurotransmitter release. However, its role in central blood pressure regulation is unknown. In the present study, blockade of the Rho/Rho-kinase pathway in the nucleus tractus solitarii (NTS) of the brain stem by microinjection of a specific Rho-kinase inhibitor decreased blood pressure, heart rate, and renal sympathetic nerve activity in both Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). However, the magnitude of decreases in these variables was greater in SHR than in WKY rats. In addition, an adenovirus vector encoding dominant-negative Rho-kinase decreased blood pressure, heart rate, and urinary norepinephrine excretion in both WKY rats and SHR in an awake and free-moving state. The magnitude of decreases in these variables was also greater in SHR than in WKY rats. Furthermore, membrane RhoA expression and Rho-kinase activity in the NTS were enhanced in SHR compared with WKY rats. These observations indicate that the Rho/Rho-kinase pathway in the NTS contributes to blood pressure regulation via the sympathetic nervous system in vivo and suggest that activation of this pathway is involved in the central mechanisms of hypertension.
Key Words: blood pressure • heart rate • sympathetic nervous system • hypertension • brain
This article has been cited by other articles:
 |
|
 |
|
  Q. Zhang, F. Yao, S. T. O'Rourke, S. Y. Qian, and C. Sun Angiotensin II enhances GABAB receptor-mediated responses and expression in nucleus tractus solitarii of rats Am J Physiol Heart Circ Physiol, November 1, 2009; 297(5): H1837 - H1844. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
F. Yao, C. Sumners, S. T. O'Rourke, and C. Sun Angiotensin II increases GABAB receptor expression in nucleus tractus solitarii of rats Am J Physiol Heart Circ Physiol, June 1, 2008; 294(6): H2712 - H2720. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Desjardins, B. Sekkali, W. Verreth, M. Pelat, D. De Keyzer, A. Mertens, G. Smith, M.-C. Herregods, P. Holvoet, and J.-L. Balligand Rosuvastatin increases vascular endothelial PPAR{gamma} expression and corrects blood pressure variability in obese dyslipidaemic mice Eur. Heart J., January 1, 2008; 29(1): 128 - 137. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. E. Kutcher, A. Y. Kolyada, H. K. Surks, and I. M. Herman Pericyte Rho GTPase Mediates Both Pericyte Contractile Phenotype and Capillary Endothelial Growth State Am. J. Pathol., August 1, 2007; 171(2): 693 - 701. [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]
|
|
|
|
 |
|
 C. Doe, R. Bentley, D. J. Behm, R. Lafferty, R. Stavenger, D. Jung, M. Bamford, T. Panchal, E. Grygielko, L. L. Wright, et al. Novel Rho Kinase Inhibitors with Anti-inflammatory and Vasodilatory Activities J. Pharmacol. Exp. Ther., January 1, 2007; 320(1): 89 - 98. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. H. Zucker Novel Mechanisms of Sympathetic Regulation in Chronic Heart Failure Hypertension, December 1, 2006; 48(6): 1005 - 1011. [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]
|
|
|
|
 |
|
 R. Alemany, O. Vogler, S. Teres, C. Egea, C. Baamonde, F. Barcelo, C. Delgado, K. H. Jakobs, and P. V. Escriba Antihypertensive action of 2-hydroxyoleic acid in SHRs via modulation of the protein kinase A pathway and Rho kinase J. Lipid Res., August 1, 2006; 47(8): 1762 - 1770. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. S. Naik, L. Xiang, and R. L. Hester Enhanced role for RhoA-associated kinase in adrenergic-mediated vasoconstriction in gracilis arteries from obese Zucker rats Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2006; 290(1): R154 - R161. [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]
|
|
|
|
|
|
K. Ito, Y. Hirooka, Y. Sagara, Y. Kimura, K. Kaibuchi, H. Shimokawa, A. Takeshita, and K. Sunagawa Inhibition of Rho-Kinase in the Brainstem Augments Baroreflex Control of Heart Rate in Rats Hypertension, October 1, 2004; 44(4): 478 - 483. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Ito, Y. Hirooka, T. Kishi, Y. Kimura, K. Kaibuchi, H. Shimokawa, and A. Takeshita Rho/Rho-Kinase Pathway in the Brainstem Contributes to Hypertension Caused by Chronic Nitric Oxide Synthase Inhibition Hypertension, February 1, 2004; 43(2): 156 - 162. [Abstract] [Full Text] [PDF]
|
|