KCa and KV channels modulate the venoarteriolar reflex in non-glabrous human skin with no roles of KATP channels, NOS, and COX

Abstract

The venoarteriolar reflex is a local mechanism that induces vasoconstriction during venous congestion in various tissues, including skin. This response is thought to play a critical role in minimizing capillary damage or edema resulting from overperfusion, though factors that modulate this response remain largely unknown. Here, we hypothesized that nitric oxide synthase (NOS), cyclooxygenase (COX), and Ca²⁺-activated, ATP-sensitive, and voltage-gated K⁺ channels (K_Ca, K_ATP, and K_V channels, respectively) modulate the venoarteriolar reflex in human skin. Cutaneous blood flow (laser-Doppler flowmetry) was monitored during a 3-min pre-occlusion baseline and following a 3-min venous occlusion of 45 mmHg, the latter maneuver was used to induce the venoarteriolar reflex. The venoarteriolar reflex was assessed at the following forearm skin sites: Experiment 1 (n = 11): 1) lactated Ringer solution (Control), 2) 10 mM N^ω-nitro-_L-arginine (NOS inhibitor), 3) 10 mM ketorolac (COX inhibitor), and 4) combined NOS + COX inhibition; Experiment 2 (n = 15): 1) lactated Ringer solution (Control), 2) 50 mM tetraethylammonium (K_Ca channel blocker), 3) 5 mM glybenclamide (K_ATP channel blocker), and 4) 10 mM 4-aminopyridine (K_V channel blocker). Separate and combined NOS and COX inhibition as well as K_ATP channel blocker had no effect on venoarteriolar reflex. Conversely, venoarteriolar reflex was attenuated by K_Ca channel blockade (36-38%) and augmented by K_V channel blockade (38-55%). We showed that K_Ca and K_V channels modulate the venoarteriolar reflex with minimum roles of NOS, COX, and K_ATP channels in human non-glabrous forearm skin in vivo. Thus, cutaneous venoarteriolar reflex changes could reflect altered K⁺ channel function.

Keywords: Dermatology; Endothelium; Heat loss responses; Hyperpolarization; Ligand-gated ion channels.