Tempol improves cutaneous thermal hyperemia through increasing nitric oxide bioavailability in young smokers*
Am J Physiol Heart Circ Physiol. 2014 Jun 1;306(11):H1507-11.
Fujii N1, Brunt VE1, Minson CT1
1Department of Human Physiology, The University of Oregon, Eugene, Oregon.
We recently found that young cigarette smokers display cutaneous vascular dysfunction relative to non-smokers, 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 years with an average daily consumption of 9.1±0.7 cigarettes, were tested. Cutaneous vascular conductance (CVC) during local heating to 42ºC at a rate of 0.1ºC/sec was evaluated as laser-Doppler flux divided by mean arterial blood pressure and normalized to maximal CVC, induced by local heating to 44ºC 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: 1) Ringer’s (control), 2) 10μM 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (Tempol), a superoxide dismutase mimetic, 3) 10mM Nω-Nitro-L-arginine (L-NNA), a non-specific NOS inhibitor, and 4) a combination of 10μM Tempol and 10mM L-NNA.
Tempol increased the plateau CVC compared with the Ringer’s site (90.0±2.3 vs. 77.6±3.9%max, P=0.028). Plateau CVC at the combination site (56.8±4.5%max) was lower than the Ringer’s site (P<0.001), and was not different from the L-NNA site (55.1±4.6%max) (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.