title: Tempol improves cutaneous thermal hyperemia through increasing nitric oxide bioavailability in young smokers.
abstract: We recently found that young cigarette smokers display cutaneous vascular dysfunction relative to nonsmokers, which is partially due to reduced nitric oxide (NO) synthase (NOS)-dependent vasodilation. In this study, we tested the hypothesis that reducing oxidative stress improves NO bioavailability, enhancing cutaneous vascular function in young smokers. Ten healthy young male smokers, who had smoked for 6.3 ± 0.7 yr with an average daily consumption of 9.1 ± 0.7 cigarettes, were tested. Cutaneous vascular conductance (CVC) during local heating to 42°C at a rate of 0.1°C/s was evaluated as laser-Doppler flux divided by mean arterial blood pressure and normalized to maximal CVC, induced by local heating to 44°C plus sodium nitroprusside administration. We evaluated plateau CVC during local heating, which is known to be highly dependent on NO, at four intradermal microdialysis sites with 1) Ringer solution (control); 2) 10 μM 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (tempol), a superoxide dismutase mimetic; 3) 10 mM N(ω)-nitro-l-arginine (l-NNA), a nonspecific NOS inhibitor; and 4) a combination of 10 μM tempol and 10 mM l-NNA. Tempol increased plateau CVC compared with the Ringer solution site (90.0 ± 2.3 vs. 77.6 ± 3.9%maximum, P = 0.028). Plateau CVC at the combination site (56.8 ± 4.5%maximum) was lower than the Ringer solution site (P < 0.001) and was not different from the l-NNA site (55.1 ± 4.6%maximum, P = 0.978), indicating the tempol effect was exclusively NO dependent. These data suggest that in young smokers, reducing oxidative stress improves cutaneous thermal hyperemia to local heating by enhancing NO production.
authors.affiliation: Department of Human Physiology, The University of Oregon, Eugene, Oregon.
authors.forename: Naoto
authors.initials: N
authors.lastname: Fujii
authors.affiliation: Department of Human Physiology, The University of Oregon, Eugene, Oregon.
authors.forename: Vienna E
authors.initials: VE
authors.lastname: Brunt
authors.affiliation: Department of Human Physiology, The University of Oregon, Eugene, Oregon minson@uoregon.edu.
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Minson
mesh_terms: D000328:Adult; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D001783:Blood Flow Velocity / Q000187:drug effects; D003497:Cyclic N-Oxides / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D006940:Hyperemia / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D012039:Regional Blood Flow / Q000187:drug effects; D012867:Skin / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism; D012907:Smoking / Q000009:adverse effects*; D013113:Spin Labels; D016896:Treatment Outcome
chemical_list: D000975:Antioxidants; D003497:Cyclic N-Oxides; D013113:Spin Labels; D009569:Nitric Oxide; C001803:tempol
keywords: free radicals; microcirculation; reactive oxygen species; skin; tobacco