Potassium Channels Mediate Hydrogen Sulfide‐induced Cutaneous Vasodilation in Healthy Young Adults

Preclinical models of cardiovascular disease suggest that hydrogen sulfide (H 2 S) is an endothelium‐derived hyperpolarizing factor that modulates vascular function via potassium (K + ) channel activation. Exogenous H 2 S donors elicit cutaneous vasodilation in young adults; however, the specific mechanism(s) underlying H 2 S‐induced cutaneous vasodilation remain unclear. The aim of this study was to examinethe specific K + channel(s) that mediate H 2 S‐induced vasodilation in the cutaneous circulation of healthy adults. Five microdialysis fibers were placed in the ventral forearm skin of 6 healthy adults (25 ± 3 yrs) for the local delivery of Ringers solution (control), 5 mM glybenclamide (GLY: K ATP channel inhibitor), 1 mM senicapoc (SENI: K Ca intermediate channel inhibitor), 50 mM tetraethylammonium (TEA: non‐specific K Ca channel inhibitor) and GLY + SENI + TEA. Laser‐Doppler flowmetry was used to continuously measure red blood cell flux. After a stable baseline, 5 mM Na 2 S (fast‐acting H 2 S donor) was perfused through all fibers to elicit H 2 S‐induced vasodilation. Data were normalized to maximal cutaneous vascular conductance (%CVC max = laser‐Doppler flux/ mean arterial pressure; 28 mM sodium nitroprusside) and expressed as a percentage increase from baseline. Na 2 S‐induced cutaneous vasodilation (Δ base 28±8 %CVC max ; P<0.05). TEA (Δ base 4±3 %CVC max ) and GLY + SENI + TEA (Δ base 5±2 %CVC max ) blunted Na 2 S‐induced cutaneous vasodilation (both P<0.05), whereas GLY (Δ base18±8 %CVC max ) or SENI alone (Δ base 22±7 %CVC max ) had no effect (both P>0.05). These data suggest that exogenous H 2 S‐induced cutaneous vasodilation is mediated by TEA‐sensitiveK Ca channels, but not by K ATP or intermediate K Ca channels, in healthy humans. NIH RO1 HL093238.