Evidence for a functional vasodilatatory role for hydrogen sulphide in the human cutaneous microvasculature

The present study aimed to identify the presence of cystathionine-γ-lyase (CSE) and 3-mercaptopyruvate sulphurtransferase (3-MST), which endogenously produce hydrogen sulphide (H₂S), and to functionally examine the mechanisms of H₂S-induced vasodilatation in the human cutaneous microcirculation. CSE and 3-MST were quantified in forearm skin samples from 5 healthy adults (24 ± 3 years) using western blot analysis. For functional studies, microdialysis fibres were placed in the forearm skin of 12 healthy adults (25 ± 3 years) for graded infusions (0.01-100 mm) of sodium sulphide (Na₂S) and sodium hydrogen sulphide (NaHS). To define the mechanisms mediating H₂S-induced vasodilatation, microdialysis fibres were perfused with Ringer solution (control), a ATP-sensitive potassium channel (K_ATP) inhibitor, an intermediate calcium-dependent potassium channel (K_Ca) inhibitor, a non-specific K_Ca channel inhibitor or triple blockade. To determine the interaction of H₂S-mediated vasodilatation with nitric oxide (NO) and cyclo-oxygenase (COX) signalling pathways, microdialysis fibres were perfused with Ringer solution (control), a non-specific NO synthase inhibitor, a non-selective COX inhibitor or combined inhibition during perfusion of increasing doses of Na₂S. CSE and 3-MST were expressed in all skin samples. Na₂S and NaHS elicited dose-dependent vasodilatation. Non-specific K_Ca channel inhibition and triple blockade blunted Na₂S-induced vasodilatation (P < 0.05), whereas K_ATP and intermediate K_Ca channel inhibition had no effect (P > 0.05). Separate and combined inhibition of NO and COX attenuated H₂S-induced vasodilatation (all P < 0.05). CSE and 3-MST are expressed in the human microvasculature. Exogenous H₂S elicits cutaneous vasodilatation mediated by K_Ca channels and has a functional interaction with both NO and COX vasodilatatory signalling pathways.