H2SIncreases Blood Pressure via Activation of L-Type Calcium Channels with Mediation by HS•Generated from Reactions with Oxyhemoglobin.

Abstract

Although the gasotransmitter hydrogen sulfide (H2S) is well known for its vasodilatory effects, H2S also exhibits vasoconstricting properties. Herein, it is demonstrated that administration of H2S as intravenous sodium sulfide (Na2S) increased blood pressure in sheep and rats, and this effect persisted after H2S has disappeared from the blood. Inhibition of the L-type calcium channel (LTCC) diminished the hypertensive effects. Incubation of Na2S with whole blood, red blood cells, methemoglobin, or oxyhemoglobin produced a hypertensive product of H2S, which is not hydrogen thioperoxide, metHb-SH- complexes, per-/poly- sulfides, or thiolsulfate, but rather a labile intermediate. One-electron oxidation of H2S by oxyhemoglobin generated its redox cousin, sulfhydryl radical (HS•). Consistent with the role of HS• as the hypertensive intermediate, scavenging HS• inhibited Na2S-induced vasoconstriction and activation of LTCCs. In conclusion, H2S causes vasoconstriction that is dependent on the activation of LTCCs and generation of HS• by oxyhemoglobin.