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