Published online before print October 6, 2005, doi: 10.1161/01.ATV.0000189304.32725.bd
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
© 2005 American Heart Association, Inc.
Atherosclerosis and Lipoproteins |
Smoking, Endothelial Function, and Rho-Kinase in Humans
From the Department of Cardiovascular Physiology and Medicine (K.N., C.G., K.N., T.U., D.J., M.Y., Y.H.), Department of Medicine and Molecular Science (K.H., M.K., K.C.), and Department of Clinical Laboratory Medicine (T.O.), Graduate School of Biomedical Sciences, Hiroshima University, Department of Developmental Biology (K.N.), Research Institute for Radiation Biology and Medicine, Japan.
Correspondence to Yukihito Higashi, MD, PhD, FAHA, Department of Cardiovascular Physiology and Medicine, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan. E-mail yhigashi{at}hiroshima-u.ac.jp
Objective— Smoking is associated with endothelial dysfunction and activated Rho-kinase in vascular smooth muscle cells (VSMCs) in humans. The purpose of this study was to elucidate the relationship between endothelial function and Rho-kinase activity in forearm VSMCs in healthy young men.
Methods and Results— We evaluated the forearm blood flow (FBF) responses to acetylcholine (ACh), fasudil, a Rho-kinase inhibitor, and sodium nitroprusside (SNP) in male smokers (n=10) and nonsmokers (n=14). FBF was measured by using a strain-gauge plethysmography. The vasodilatory effect of ACh was significantly smaller in smokers than that in nonsmokers. The vasodilatory effect of fasudil was significantly greater in smokers than that in nonsmokers. The vasodilatory effects of SNP in the 2 groups were similar. There was a significant correlation between the maximal FBF response to fasudil and that to ACh (r=–0.67; P<0.01). There was no significant correlation between the maximal FBF response to fasudil and that to SNP. The intra-arterial coinfusion of fasudil significantly increased the FBF response to ACh in smokers but not in nonsmokers. There were no significant differences between FBF response to fasudil alone and that in combination with NG-monomethyl-L-arginine in smokers and in nonsmokers. The intra-arterial coinfusion ascorbic acid did not alter the FBF response to fasudil in both groups.
Conclusions— These findings suggest that smoking is involved in not only endothelial dysfunction but also activation of Rho-kinase in VSMCs in forearm circulation, and that there is a significant correlation between endothelial function and Rho-kinase activity in VSMCs.
Smoking is associated with endothelial dysfunction and activated Rho-kinase in vascular smooth muscle cells (VSMCs) in humans. The purpose of this study was to elucidate the relationship between endothelial function and Rho-kinase activity in forearm VSMCs in healthy young men. Our findings suggest that smoking is involved in not only endothelial dysfunction but also activation of Rho-kinase in VSMCs in forearm circulation, and that there is a significant correlation between endothelial function and Rho-kinase activity in VSMCs.
Key Words: smoking • Rho-kinase • endothelial function • vascular smooth muscle cell • healthy young man
This article has been cited by other articles:
 |
|
 |
|
  T. R. Richens, D. J. Linderman, S. A. Horstmann, C. Lambert, Y.-Q. Xiao, R. L. Keith, D. M. Boe, K. Morimoto, R. P. Bowler, B. J. Day, et al. Cigarette Smoke Impairs Clearance of Apoptotic Cells through Oxidant-dependent Activation of RhoA Am. J. Respir. Crit. Care Med., June 1, 2009; 179(11): 1011 - 1021. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Sumiyoshi, H. Mokuno, T. Iesaki, K. Shimada, T. Miyazaki, A. Kume, T. Kiyanagi, K. Kuremoto, Y. Watanabe, N. Tada, et al. Deletion of the Fc receptors {gamma} chain preserves endothelial function affected by hypercholesterolaemia in mice fed on a high-fat diet Cardiovasc Res, December 1, 2008; 80(3): 463 - 470. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Iida, M. Iida, M. Takenaka, N. Fukuoka, and S. Dohi Rho-kinase inhibitor and Nicotinamide Adenine Dinucleotide PHosphate oxidase inhibitor prevent impairment of endothelium-dependent cerebral vasodilation by acute cigarette smoking in rats Journal of Renin-Angiotensin-Aldosterone System, June 1, 2008; 9(2): 89 - 94. [Abstract] [PDF]
|
|
|
|
 |
|
 S. de Ferranti and D. Mozaffarian The Perfect Storm: Obesity, Adipocyte Dysfunction, and Metabolic Consequences Clin. Chem., June 1, 2008; 54(6): 945 - 955. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. L. Ding and F. B. Hu Smoking and Type 2 Diabetes: Underrecognized Risks and Disease Burden JAMA, December 12, 2007; 298(22): 2675 - 2676. [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]
|
|
|
|
 |
|
 P.-Y. Liu, J.-H. Chen, L.-J. Lin, and J. K. Liao Increased Rho Kinase Activity in a Taiwanese Population With Metabolic Syndrome J. Am. Coll. Cardiol., April 17, 2007; 49(15): 1619 - 1624. [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]
|
|
|
|
 |
|
 W. S. Waring, J. A. McKnight, D. J. Webb, and S. R.J. Maxwell Uric Acid Restores Endothelial Function in Patients With Type 1 Diabetes and Regular Smokers Diabetes, November 1, 2006; 55(11): 3127 - 3132. [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]
|
|