Tetraethylammonium, glibenclamide, and 4‐aminopyridine modulate post‐occlusive reactive hyperemia in non‐glabrous human skin with no roles of NOS and COX. (12th September 2019) - Fujii, Naoto
Abstract: 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 (KC a, KATP, and KV 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 KC a channel blocker), (c) 5 mM glibenclamide (non‐specific KATP channel blocker), and (d) 10 mM 4‐aminopyridine (non‐selective KV 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.