Tetraethylammonium, glibenclamide, and 4‐aminopyridine modulate post‐occlusive reactive hyperemia in non‐glabrous human skin with no roles of NOS and COX

Objectives Post‐occlusive reactive hyperemia ( PORH ) following arterial occlusion is widely used to assess cutaneous microvascular function, though the underlying mechanisms remain to be fully elucidated. We evaluated the hypothesis that Ca 2+ ‐activated, ATP ‐sensitive, and voltage‐gated K + channels ( K C a , K ATP , and K V channels, respectively) contribute to PORH while nitric oxide synthase ( NOS ) and cyclooxygenase ( COX ) do not. Methods On separate occasions, cutaneous blood flow (laser Doppler flowmetry) was monitored before and following 5‐min arterial occlusion at forearm skin sites treated via microdialysis with the following: Experiment 1 (n = 11): (a) lactated Ringer solution (Control), (b) 10 mM N ω ‐nitro‐ L ‐arginine ( NOS inhibitor), (c) 10 mM ketorolac ( COX inhibitor), and (d) combined NOS + COX inhibition; Experiment 2 (n = 14): (a) lactated Ringer solution (Control), (b) 50 mM tetraethylammonium (non‐selective K C a channel blocker), (c) 5 mM glibenclamide (non‐specific K ATP channel blocker), and (d) 10 mM 4‐aminopyridine (non‐selective K V channel blocker). Results Separate and combined NOS and COX inhibition did not influence PORH . Conversely, tetraethylammonium and glibenclamide attenuated, whereas 4‐aminopyridine augmented PORH . Conclusions We showed that tetraethylammonium, glibenclamide, and 4‐aminopyridine modulate PORH with no roles of NOS and COX in human non‐glabrous forearm skin in vivo. Thus, cutaneous PORH changes could reflect altered K + channel function.