title: Cigarette smoking abolishes ischemic preconditioning-induced augmentation of endothelium-dependent vasodilation.
abstract: We have shown recently that repetition of ischemic preconditioning stimulus augments endothelium-dependent vasodilation in forearm circulation of healthy subjects through increases in NO production and the number of circulating progenitor cells under a local condition. The purpose of this study was to evaluate the "late" effect of ischemic preconditioning on endothelial function in smokers. Ischemic preconditioning was induced by upper-limb ischemia 6 times a day for 1 month. We evaluated forearm blood flow responses to acetylcholine and sodium nitroprusside before and after ischemic preconditioning stimulus in 15 male smokers (27+/-7 years) and 15 male nonsmokers (26+/-5 years). Forearm blood flow was measured by using a strain-gauge plethysmography. The ischemic preconditioning stimulus resulted in significant increases in the circulating level of circulating progenitor cells from 1029+/-261 to 1232+/-341 mL (P=0.02), cell migration response to vascular endothelial growth factor from 38+/-16 to 52+/-17 per high-power field (P=0.02), and forearm blood flow response to acetylcholine from 25.1+/-5.2 to 32.4+/-6.6 mL/min per 100 mL of tissue (P=0.002) in nonsmokers, but these did not change in the smoker group. The forearm blood flow responses to sodium nitroprusside before and after the ischemic preconditioning stimulus were similar. Intra-arterial infusion of N(G)-monomethyl-l-arginine, an NO synthase inhibitor, completely eliminated the ischemic preconditioning stimulus-induced augmentation of forearm blood flow responses to acetylcholine in nonsmokers. These findings suggest that repetition of ischemic preconditioning stimulus may be a simple, safe, and feasible therapeutic technique for endothelial protection of peripheral vessels. However, smoking abolishes ischemic preconditioning stimulus-induced augmentation of endothelium-dependent vasodilation.
authors.affiliation: Department of Cardiovascular Physiology and Medicine, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Mimami-ku, Hiroshima 734-8551, Japan. yhigashi@hiroshima-u.ac.jp
authors.forename: Shuji
authors.initials: S
authors.lastname: Nakamura
authors.forename: Masashi
authors.initials: M
authors.lastname: Kimura
authors.forename: Chikara
authors.initials: C
authors.lastname: Goto
authors.forename: Kensuke
authors.initials: K
authors.lastname: Noma
authors.forename: Masao
authors.initials: M
authors.lastname: Yoshizumi
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Chayama
authors.forename: Yasuki
authors.initials: Y
authors.lastname: Kihara
authors.forename: Yukihito
authors.initials: Y
authors.lastname: Higashi
mesh_terms: D000109:Acetylcholine / Q000008:administration & dosage; D000328:Adult; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D005542:Forearm / Q000098:blood supply; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000502:physiology; D006801:Humans; D007261:Infusions, Intra-Arterial; D007511:Ischemia / Q000503:physiopathology*; D019194:Ischemic Preconditioning; D008297:Male; D019335:Nitroarginine / Q000008:administration & dosage; D009599:Nitroprusside / Q000008:administration & dosage; D010991:Plethysmography; D012907:Smoking / Q000009:adverse effects*; D042461:Vascular Endothelial Growth Factor A / Q000097:blood; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000008:administration & dosage; D055815:Young Adult
chemical_list: D004791:Enzyme Inhibitors; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D014665:Vasodilator Agents; D009599:Nitroprusside; D019335:Nitroarginine; D000109:Acetylcholine