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

Taiming Liu; Meijuan Zhang; Shawn Hanson; Rucha Juarez; Sean Wilson; Hobe Schroeder; Qian Li; Lingchao Zhu; Guangyu Zhang; Arlin B Blood

doi:10.1002/advs.202305866

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

Adv Sci (Weinh). 2024 Apr 29:e2305866. doi: 10.1002/advs.202305866. Online ahead of print.

Authors

Taiming Liu¹, Meijuan Zhang¹, Shawn Hanson², Rucha Juarez², Sean Wilson², Hobe Schroeder², Qian Li³, Lingchao Zhu⁴, Guangyu Zhang⁵, Arlin B Blood^{1

2}

Affiliations

¹ Division of Neonatology, Department of Pediatrics, Loma Linda University School of Medicine, Loma Linda, CA, 92354, USA.
² Lawrence D. Longo Center for Perinatal Biology, Loma Linda University School of Medicine, Loma Linda, CA, 92354, USA.
³ Department of Medicine, Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, AL, 35294, UK.
⁴ Department of Chemistry, University of California, Riverside, CA, 92521, USA.
⁵ Mass spectrometry core facility, Loma Linda University, Loma Linda, CA, 92354, USA.

PMID: 38685626
DOI: 10.1002/advs.202305866

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.

Keywords: L‐type calcium channel; blood pressure; hemoglobin; hydrogen sulfide; thiyl radical; vasoconstriction.

Grants and funding

R01HL155295/GF/NIH HHS/United States