H2S Increases Blood Pressure via Activation of L‐Type Calcium Channels with Mediation by HS• Generated from Reactions with Oxyhemoglobin

Abstract Although the gasotransmitter hydrogen sulfide (H 2 S) is well known for its vasodilatory effects, H 2 S also exhibits vasoconstricting properties. Herein, it is demonstrated that administration of H 2 S as intravenous sodium sulfide (Na 2 S) increased blood pressure in sheep and rats, and this effect persisted after H 2 S has disappeared from the blood. Inhibition of the L‐type calcium channel (LTCC) diminished the hypertensive effects. Incubation of Na 2 S with whole blood, red blood cells, methemoglobin, or oxyhemoglobin produced a hypertensive product of H 2 S, which is not hydrogen thioperoxide, metHb‐SH − complexes, per‐/poly‐ sulfides, or thiolsulfate, but rather a labile intermediate. One‐electron oxidation of H 2 S by oxyhemoglobin generated its redox cousin, sulfhydryl radical (HS • ) . Consistent with the role of HS • as the hypertensive intermediate, scavenging HS • inhibited Na 2 S‐induced vasoconstriction and activation of LTCCs. In conclusion, H 2 S causes vasoconstriction that is dependent on the activation of LTCCs and generation of HS • by oxyhemoglobin.