title: 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.
authors.affiliation: Department of Cardiovascular Physiology and Medicine, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan.
authors.forename: Kensuke
authors.initials: K
authors.lastname: Noma
authors.forename: Yukihito
authors.initials: Y
authors.lastname: Higashi
authors.forename: Daisuke
authors.initials: D
authors.lastname: Jitsuiki
authors.forename: Keiko
authors.initials: K
authors.lastname: Hara
authors.forename: Masashi
authors.initials: M
authors.lastname: Kimura
authors.forename: Keigo
authors.initials: K
authors.lastname: Nakagawa
authors.forename: Chikara
authors.initials: C
authors.lastname: Goto
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Oshima
authors.forename: Masao
authors.initials: M
authors.lastname: Yoshizumi
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Chayama
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000293:Adolescent; D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005542:Forearm / Q000098:blood supply*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000201:enzymology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009599:Nitroprusside / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012039:Regional Blood Flow / Q000187:drug effects; D012907:Smoking; D014665:Vasodilator Agents / Q000494:pharmacology; D019323:omega-N-Methylarginine / Q000494:pharmacology; D054460:rho-Associated Kinases
chemical_list: D004791:Enzyme Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D014665:Vasodilator Agents; D009599:Nitroprusside; D019323:omega-N-Methylarginine; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D019001:Nitric Oxide Synthase; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; C049347:fasudil