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 -activated, ATP-sensitive, and voltage-gated K channels (K , K , and K 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 -nitro- -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 channel blocker), (c) 5 mM glibenclamide (non-specific K channel blocker), and (d) 10 mM 4-aminopyridine (non-selective K 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.