Circulation Research. 2001
Published online before print April 13, 2001, doi: 10.1161/hh0801.090441
Published online before print April 13, 2001, doi: 10.1161/hh0801.090441
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
© 2001 American Heart Association, Inc.
Article |
Evidence That Rho-Kinase Activity Contributes to Cerebral Vascular Tone In Vivo and Is Enhanced During Chronic Hypertension
Comparison With Protein Kinase C
From the Department of Pharmacology, The University of Melbourne, Parkville, Victoria, Australia.
Correspondence to Christopher G. Sobey, PhD, Department of Pharmacology, The University of Melbourne, Grattan St, Parkville, Victoria 3010, Australia. E-mail cgsobey{at}unimelb.edu.au
Abstract
Abstract—The small G protein Rho and its target Rho-kinase may participate in the mechanisms underlying vascular contractile tone via inhibition of myosin light chain phosphatase. The present study has tested the hypothesis that Rho-kinase activity normally contributes to cerebral vascular tone in vivo, and that this effect is augmented during chronic hypertension. Comparative studies also examined the role of protein kinase C (PKC) in regulation of cerebral artery tone. Two Rho-kinase inhibitors, Y-27632 (0.1 to 100 µmol/L) and HA1077 (1 to 10 µmol/L), caused marked concentration-dependent increases in basilar artery diameter of anesthetized normotensive rats (Sprague-Dawley and Wistar-Kyoto [WKY] strains), as measured using a cranial window approach. By comparison, the selective PKC inhibitors calphostin C (0.01 to 0.5 µmol/L) and Ro 31-8220 (5 µmol/L) had little or no effect on basilar artery diameter. Vasodilator responses to Y-27632 were unaffected by PKC inhibition or activation. In two models of chronic hypertension (spontaneously hypertensive rats and WKY rats treated with N-nitro-L-arginine methyl ester for 4 weeks), Y-27632 elicited cerebral vasodilator responses that were significantly greater than in control WKY rats (P<0.05), indicating that the chronically hypertensive state and not genetic factors contributed to the increased responses to Rho-kinase inhibition. PKC inhibition had no significant effect on basilar artery diameter in chronically hypertensive rats. These data suggest that Rho-kinase, but not PKC, activity contributes substantially to cerebral artery tone in vivo, and this effect is augmented in the cerebral circulation during chronic hypertension.
Key Words: cerebral artery • hypertension • protein kinase C • Rho-kinase
This article has been cited by other articles:
 |
|
 |
|
  Y. Chiba, S. Nakazawa, M. Todoroki, K. Shinozaki, H. Sakai, and M. Misawa Interleukin-13 Augments Bronchial Smooth Muscle Contractility with an Up-Regulation of RhoA Protein Am. J. Respir. Cell Mol. Biol., February 1, 2009; 40(2): 159 - 167. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Chiba, J. Arima, H. Sakai, and M. Misawa Lovastatin inhibits bronchial hyperresponsiveness by reducing RhoA signaling in rat allergic asthma Am J Physiol Lung Cell Mol Physiol, April 1, 2008; 294(4): L705 - L713. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. L. Corteling, S. E. Brett, H. Yin, X.-L. Zheng, M. P. Walsh, and D. G. Welsh The functional consequence of RhoA knockdown by RNA interference in rat cerebral arteries Am J Physiol Heart Circ Physiol, July 1, 2007; 293(1): H440 - H447. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. A. Miller, G. R. Drummond, A. E. Mast, H. H.H.W. Schmidt, and C. G. Sobey Effect of Gender on NADPH-Oxidase Activity, Expression, and Function in the Cerebral Circulation: Role of Estrogen Stroke, July 1, 2007; 38(7): 2142 - 2149. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Chrissobolis and C. G. Sobey Recent Evidence for an Involvement of Rho-Kinase in Cerebral Vascular Disease Stroke, August 1, 2006; 37(8): 2174 - 2180. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Li, K. Witte, M. August, I. Brausch, U. Godtel-Armbrust, A. Habermeier, E. I. Closs, M. Oelze, T. Munzel, and U. Forstermann Reversal of Endothelial Nitric Oxide Synthase Uncoupling and Up-Regulation of Endothelial Nitric Oxide Synthase Expression Lowers Blood Pressure in Hypertensive Rats J. Am. Coll. Cardiol., June 20, 2006; 47(12): 2536 - 2544. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Budzyn, M. Paull, P. D. Marley, and C. G. Sobey Segmental Differences in the Roles of Rho-Kinase and Protein Kinase C in Mediating Vasoconstriction J. Pharmacol. Exp. Ther., May 1, 2006; 317(2): 791 - 796. [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]
|
|
|
|
 |
|
 J. H. Brown, D. P. Del Re, and M. A. Sussman The Rac and Rho Hall of Fame: A Decade of Hypertrophic Signaling Hits Circ. Res., March 31, 2006; 98(6): 730 - 742. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Chiba, M. Murata, H. Ushikubo, Y. Yoshikawa, A. Saitoh, H. Sakai, J. Kamei, and M. Misawa Effect of Cigarette Smoke Exposure In Vivo on Bronchial Smooth Muscle Contractility In Vitro in Rats Am. J. Respir. Cell Mol. Biol., December 1, 2005; 33(6): 574 - 581. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. P. R. Jarajapu and H. J. Knot Relative contribution of Rho kinase and protein kinase C to myogenic tone in rat cerebral arteries in hypertension Am J Physiol Heart Circ Physiol, November 1, 2005; 289(5): H1917 - H1922. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Budzyn, P. D. Marley, and C. G. Sobey Opposing Roles of Endothelial and Smooth Muscle Phosphatidylinositol 3-Kinase in Vasoconstriction: Effects of Rho-Kinase and Hypertension J. Pharmacol. Exp. Ther., June 1, 2005; 313(3): 1248 - 1253. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Rajasekaran, S. White, A. Baquir, and N. Wilkes Rho-kinase Inhibition Improves Erectile Function in Aging Male Brown-Norway Rats J Androl, March 1, 2005; 26(2): 182 - 188. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Nagaoka, K. A. Fagan, S. A. Gebb, K. G. Morris, T. Suzuki, H. Shimokawa, I. F. McMurtry, and M. Oka Inhaled Rho Kinase Inhibitors Are Potent and Selective Vasodilators in Rat Pulmonary Hypertension Am. J. Respir. Crit. Care Med., March 1, 2005; 171(5): 494 - 499. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Loirand, M. Rolli-Derkinderen, and P. Pacaud RhoA and resistance artery remodeling Am J Physiol Heart Circ Physiol, March 1, 2005; 288(3): H1051 - H1056. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. P. Didion, C. M. Lynch, G. L. Baumbach, and F. M. Faraci Impaired Endothelium-Dependent Responses and Enhanced Influence of Rho-Kinase in Cerebral Arterioles in Type II Diabetes Stroke, February 1, 2005; 36(2): 342 - 347. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. M. Faraci Oxidative Stress: The Curse That Underlies Cerebral Vascular Dysfunction? Stroke, February 1, 2005; 36(2): 186 - 188. [Full Text] [PDF]
|
|
|
|
 |
|
 T. M. Seasholtz and J. H. Brown RHO SIGNALING in Vascular Diseases Mol. Interv., December 1, 2004; 4(6): 348 - 357. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Erdos, J. A. Snipes, B. Kis, A. W. Miller, and D. W. Busija Vasoconstrictor mechanisms in the cerebral circulation are unaffected by insulin resistance Am J Physiol Regulatory Integrative Comp Physiol, December 1, 2004; 287(6): R1456 - R1461. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. L. Lee, R. C. Webb, and L. Jin Hypertension and RhoA/Rho-Kinase Signaling in the Vasculature: Highlights From the Recent Literature Hypertension, December 1, 2004; 44(6): 796 - 799. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Chrissobolis, K. Budzyn, P. D. Marley, and C. G. Sobey Evidence That Estrogen Suppresses Rho-Kinase Function in the Cerebral Circulation In Vivo Stroke, September 1, 2004; 35(9): 2200 - 2205. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Budzyn, P. D. Marley, and C. G. Sobey Chronic mevastatin modulates receptor-dependent vascular contraction in eNOS-deficient mice Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2004; 287(2): R342 - R348. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. A. Wehrwein, C. A. Northcott, R. D. Loberg, and S. W. Watts Rho/Rho Kinase and Phosphoinositide 3-Kinase Are Parallel Pathways in the Development of Spontaneous Arterial Tone in Deoxycorticosterone Acetate-Salt Hypertension J. Pharmacol. Exp. Ther., June 1, 2004; 309(3): 1011 - 1019. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. P. SOMLYO and A. V. SOMLYO Ca2+ Sensitivity of Smooth Muscle and Nonmuscle Myosin II: Modulated by G Proteins, Kinases, and Myosin Phosphatase Physiol Rev, October 1, 2003; 83(4): 1325 - 1358. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Galle, A. Mameghani, S.-S. Bolz, S. Gambaryan, M. Gorg, T. Quaschning, U. Raff, H. Barth, S. Seibold, C. Wanner, et al. Oxidized LDL and its Compound Lysophosphatidylcholine Potentiate AngII-Induced Vasoconstriction by Stimulation of RhoA J. Am. Soc. Nephrol., June 1, 2003; 14(6): 1471 - 1479. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Hosaka, R. Mizuno, and T. Ohhashi Rho-Rho kinase pathway is involved in the regulation of myogenic tone and pump activity in isolated lymph vessels Am J Physiol Heart Circ Physiol, June 1, 2003; 284(6): H2015 - H2025. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Wickman, C. Lan, and B. Vollrath Functional Roles of the Rho/Rho Kinase Pathway and Protein Kinase C in the Regulation of Cerebrovascular Constriction Mediated by Hemoglobin: Relevance to Subarachnoid Hemorrhage and Vasospasm Circ. Res., April 18, 2003; 92(7): 809 - 816. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Seko, M. Ito, Y. Kureishi, R. Okamoto, N. Moriki, K. Onishi, N. Isaka, D. J. Hartshorne, and T. Nakano Activation of RhoA and Inhibition of Myosin Phosphatase as Important Components in Hypertension in Vascular Smooth Muscle Circ. Res., March 7, 2003; 92(4): 411 - 418. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Randriamboavonjy, R. Busse, and I. Fleming 20-HETE-Induced Contraction of Small Coronary Arteries Depends on the Activation of Rho-Kinase Hypertension, March 1, 2003; 41(3): 801 - 806. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Shirao, S. Kashiwagi, M. Sato, S. Miwa, F. Nakao, T. Kurokawa, N. Todoroki-Ikeda, K. Mogami, Y. Mizukami, S. Kuriyama, et al. Sphingosylphosphorylcholine Is a Novel Messenger for Rho-Kinase-Mediated Ca2+ Sensitization in the Bovine Cerebral Artery: Unimportant Role for Protein Kinase C Circ. Res., July 26, 2002; 91(2): 112 - 119. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. G. Lamping Enhanced Contractile Mechanisms in Vasospasm: Is Endothelial Dysfunction the Whole Story? Circulation, April 2, 2002; 105(13): 1520 - 1522. [Full Text] [PDF]
|
|
|
|
|
|
M. Tosaka, F. Okajima, Y. Hashiba, N. Saito, T. Nagano, T. Watanabe, T. Kimura, and T. Sasaki Sphingosine 1-Phosphate Contracts Canine Basilar Arteries In Vitro and In Vivo: Possible Role in Pathogenesis of Cerebral Vasospasm Stroke, December 1, 2001; 32(12): 2913 - 2919. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. M. Seasholtz, T. Zhang, M. R. Morissette, A. L. Howes, A. H. Yang, and J. H. Brown Increased Expression and Activity of RhoA Are Associated With Increased DNA Synthesis and Reduced p27Kip1 Expression in the Vasculature of Hypertensive Rats Circ. Res., September 14, 2001; 89(6): 488 - 495. [Abstract] [Full Text] [PDF]
|
|