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Smoking activates rho-kinase in smooth muscle cells of forearm vasculature in humans.

Abstract
Previous studies have shown that smoking is strongly associated with atherosclerosis and coronary vascular disease. Rho-kinase plays an important role in various cellular functions associated with atherosclerosis and hypertension. However, there is no information on the relationship between smoking and Rho-kinase activity in humans. The purpose of this study was to determine the Rho-kinase activity in forearm vascular smooth muscle cells (VSMCs) in healthy young male smokers. We evaluated the forearm blood flow (FBF) responses to fasudil (3, 10, and 30 microg/min for 5 minutes), a Rho-kinase inhibitor, or sodium nitroprusside (0.75, 1.5, and 3.0 microg/min for 5 minutes) in current smokers (n=8) and nonsmokers (n=8). FBF was measured with a strain-gauge plethysmograph. The vasodilatory effect of fasudil was significantly greater in smokers than in nonsmokers (14.9+/-3.5 versus 10.5+/-3.6 mL/min per 100 mL tissue; P<0.01). The FBF responses to sodium nitroprusside were similar in the 2 groups (34.7+/-10.4 versus 33.2+/-10.2 mL/min per 100 mL tissue; P=0.78). These findings suggest that smoking activates Rho-kinase in forearm VSMCs but does not alter the vasodilatory effect induced by exogenous nitric oxide in forearm VSMCs in healthy young men.
AuthorsKensuke Noma, Yukihito Higashi, Daisuke Jitsuiki, Keiko Hara, Masashi Kimura, Keigo Nakagawa, Chikara Goto, Tetsuya Oshima, Masao Yoshizumi, Kazuaki Chayama
JournalHypertension (Dallas, Tex. : 1979) (Hypertension) Vol. 41 Issue 5 Pg. 1102-5 (May 2003) ISSN: 1524-4563 [Electronic] United States
PMID12682081 (Publication Type: Clinical Trial, Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Enzyme Inhibitors
  • Intracellular Signaling Peptides and Proteins
  • Vasodilator Agents
  • Nitroprusside
  • omega-N-Methylarginine
  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
  • Nitric Oxide Synthase
  • Protein Serine-Threonine Kinases
  • rho-Associated Kinases
  • fasudil
Topics
  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine (analogs & derivatives, pharmacology)
  • Adolescent
  • Adult
  • Blood Pressure (drug effects)
  • Enzyme Inhibitors (pharmacology)
  • Forearm (blood supply)
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Male
  • Muscle, Smooth, Vascular (enzymology)
  • Nitric Oxide Synthase (antagonists & inhibitors)
  • Nitroprusside (pharmacology)
  • Protein Serine-Threonine Kinases (antagonists & inhibitors, metabolism)
  • Regional Blood Flow (drug effects)
  • Smoking
  • Vasodilator Agents (pharmacology)
  • omega-N-Methylarginine (pharmacology)
  • rho-Associated Kinases

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