Involvement of different K channel subtypes in hydrogen sulfide-induced vasorelaxation of human internal mammary artery.

Background: Changes in K channel expression/function are associated with disruption of vascular reactivity in several pathological conditions, including hypertension, diabetes, and atherosclerosis. Gasotransmitters achieve part of their effects in the organism by regulating ion channels, especially K channels. Their involvement in hydrogen sulfide (HS)-mediated vasorelaxation is still unclear, and data about human vessels are limited.

Objective: To determine the role of K channel subtypes in the vasorelaxant mechanism of HS donor, sodium-hydrosulfide (NaHS), on isolated human internal mammary artery (HIMA).

Results: NaHS (1 × 10-3 × 10 mol/L) induced a concentration-dependent relaxation of HIMA pre-contracted by phenylephrine and high K. Among K channel blockers, iberiotoxin, glibenclamide, 4-aminopyridine (4-AP), and margatoxin significantly inhibited NaHS-induced relaxation of phenylephrine-contracted HIMA (P < 0.01), whereas in the presence of apamin/1-[(2-chlorophenyl) diphenylmethyl]-1H-pyrazole (TRAM-34) combination, the HIMA relaxation was partially reduced (P < 0.05). The effect of NaHS was antagonized by NO pathway inhibitors, L-NAME and KT5823, and by cyclo-oxygenase inhibitor, indomethacin (P < 0.01). Under conditions of blocked NO/prostacyclin synthesis and release, apamin/TRAM-34 and glibenclamide caused further decrease in NaHS-induced vasorelaxation (P < 0.01), while iberiotoxin, 4-AP, and margatoxin were without additional effect (P > 0.05). In the presence of nifedipine, NaHS induced partial relaxation of HIMA (P < 0.01).

Conclusion: Our results demonstrated that HS donor, NaHS, induced concentration-dependent relaxation of isolated HIMA. Vasorelaxant mechanisms of HS included direct or indirect opening of different K channel subtypes, K, BK, SK/IK, and K (subtype K1.3), in addition to NO pathway activation and interference with extracellular Ca influx.