doi: 10.1161/CIRCULATIONAHA.104.510248
(Circulation. 2005;111:2741-2747.)
© 2005 American Heart Association, Inc.
Heart Failure |
Rho-Kinase Inhibitor Improves Increased Vascular Resistance and Impaired Vasodilation of the Forearm in Patients With Heart Failure
From the Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, 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
Received September 30, 2004; revision received January 20, 2005; accepted February 23, 2005.
Background— Rho-kinase is suggested to have an important role in enhanced vasoconstriction in animal models of heart failure (HF). Patients with HF are characterized by increased vasoconstriction and reduced vasodilator responses to reactive hyperemia and exercise. The aim of the present study was to examine whether Rho-kinase is involved in the peripheral circulation abnormalities of HF in humans with the Rho-kinase inhibitor fasudil.
Methods and Results— Studies were performed in patients with HF (HF group, n=26) and an age-matched control group (n=26). Forearm blood flow was measured with a strain-gauge plethysmograph during intra-arterial infusion of graded doses of fasudil or sodium nitroprusside. Resting forearm vascular resistance (FVR) was significantly higher in the HF group than in the control group. The increase in forearm blood flow evoked by fasudil was significantly greater in the HF group than in the control group. The increased FVR was decreased by fasudil in the HF group toward the level of the control group. By contrast, FVR evoked by sodium nitroprusside was comparable between the 2 groups. Fasudil significantly augmented the impaired ischemic vasodilation during reactive hyperemia after arterial occlusion of the forearm in the HF group but not in the control group. Fasudil did not augment the increased FVR evoked by phenylephrine in the control group significantly.
Conclusions— These results indicate that Rho-kinase is involved in increased FVR and impaired vasodilation of the forearm in patients with HF.
Key Words: heart failure • blood flow • vasoconstriction • vasodilation
Related Article:
Circulation 2005 111: 2711.
This article has been cited by other articles:
 |
|
 |
|
  M. Lohn, O. Plettenburg, Y. Ivashchenko, A. Kannt, A. Hofmeister, D. Kadereit, M. Schaefer, W. Linz, M. Kohlmann, J.-M. Herbert, et al. Pharmacological Characterization of SAR407899, a Novel Rho-Kinase Inhibitor Hypertension, September 1, 2009; 54(3): 676 - 683. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Holvoet and P. Sinnaeve Angio-Associated Migratory Cell Protein and Smooth Muscle Cell Migration in Development of Restenosis and Atherosclerosis J. Am. Coll. Cardiol., July 22, 2008; 52(4): 312 - 314. [Full Text] [PDF]
|
|
|
|
 |
|
 V. Kolavennu, L. Zeng, H. Peng, Y. Wang, and F. R. Danesh Targeting of RhoA/ROCK Signaling Ameliorates Progression of Diabetic Nephropathy Independent of Glucose Control Diabetes, March 1, 2008; 57(3): 714 - 723. [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]
|
|
|
|
 |
|
 E. Bussemaker, F. Pistrosch, S. Forster, K. Herbrig, P. Gross, J. Passauer, and R. P. Brandes Rho kinase contributes to basal vascular tone in humans: role of endothelium-derived nitric oxide Am J Physiol Heart Circ Physiol, July 1, 2007; 293(1): H541 - H547. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. S. Thompson-Torgerson, L. A. Holowatz, N. A. Flavahan, and W. L. Kenney Cold-induced cutaneous vasoconstriction is mediated by Rho kinase in vivo in human skin Am J Physiol Heart Circ Physiol, April 1, 2007; 292(4): H1700 - H1705. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Noma, C. Goto, K. Nishioka, D. Jitsuiki, T. Umemura, K. Ueda, M. Kimura, K. Nakagawa, T. Oshima, K. Chayama, et al. Roles of Rho-Associated Kinase and Oxidative Stress in the Pathogenesis of Aortic Stiffness J. Am. Coll. Cardiol., February 13, 2007; 49(6): 698 - 705. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Nohria, M. E. Grunert, Y. Rikitake, K. Noma, A. Prsic, P. Ganz, J. K. Liao, and M. A. Creager Rho Kinase Inhibition Improves Endothelial Function in Human Subjects With Coronary Artery Disease Circ. Res., December 8, 2006; 99(12): 1426 - 1432. [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]
|
|
|
|
 |
|
 J. Chang, M. Xie, V. R. Shah, M. D. Schneider, M. L. Entman, L. Wei, and R. J. Schwartz Activation of Rho-associated coiled-coil protein kinase 1 (ROCK-1) by caspase-3 cleavage plays an essential role in cardiac myocyte apoptosis PNAS, September 26, 2006; 103(39): 14495 - 14500. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Winaver, E. Ovcharenko, I. Rubinstein, K. Gurbanov, P. Pollesello, B. Bishara, A. Hoffman, and Z. Abassi Involvement of Rho kinase pathway in the mechanism of renal vasoconstriction and cardiac hypertrophy in rats with experimental heart failure Am J Physiol Heart Circ Physiol, May 1, 2006; 290(5): H2007 - H2014. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Noma, N. Oyama, and J. K. Liao Physiological role of ROCKs in the cardiovascular system Am J Physiol Cell Physiol, March 1, 2006; 290(3): C661 - C668. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Loirand, P. Guerin, and P. Pacaud Rho Kinases in Cardiovascular Physiology and Pathophysiology Circ. Res., February 17, 2006; 98(3): 322 - 334. [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]
|
|