Evidence for a functional vasodilatatory role for hydrogen sulphide in the human cutaneous microvasculature

Jessica L. Kutz, Jody L. Greaney, Lakshmi Santhanam, Lacy M. Alexander

Research output: Contribution to journalArticle

Abstract

The present study aimed to identify the presence of cystathionine-γ-lyase (CSE) and 3-mercaptopyruvate sulphurtransferase (3-MST), which endogenously produce hydrogen sulphide (H2S), and to functionally examine the mechanisms of H2S-induced vasodilatation in the human cutaneous microcirculation. CSE and 3-MST were quantified in forearm skin samples from 5 healthy adults (24 ± 3 years) using western blot analysis. For functional studies, microdialysis fibres were placed in the forearm skin of 12 healthy adults (25 ± 3 years) for graded infusions (0.01-100 mm) of sodium sulphide (Na2S) and sodium hydrogen sulphide (NaHS). To define the mechanisms mediating H2S-induced vasodilatation, microdialysis fibres were perfused with Ringer solution (control), a ATP-sensitive potassium channel (KATP) inhibitor, an intermediate calcium-dependent potassium channel (KCa) inhibitor, a non-specific KCa channel inhibitor or triple blockade. To determine the interaction of H2S-mediated vasodilatation with nitric oxide (NO) and cyclo-oxygenase (COX) signalling pathways, microdialysis fibres were perfused with Ringer solution (control), a non-specific NO synthase inhibitor, a non-selective COX inhibitor or combined inhibition during perfusion of increasing doses of Na2S. CSE and 3-MST were expressed in all skin samples. Na2S and NaHS elicited dose-dependent vasodilatation. Non-specific KCa channel inhibition and triple blockade blunted Na2S-induced vasodilatation (P < 0.05), whereas KATP and intermediate KCa channel inhibition had no effect (P > 0.05). Separate and combined inhibition of NO and COX attenuated H2S-induced vasodilatation (all P < 0.05). CSE and 3-MST are expressed in the human microvasculature. Exogenous H2S elicits cutaneous vasodilatation mediated by KCa channels and has a functional interaction with both NO and COX vasodilatatory signalling pathways.

Original languageEnglish (US)
Pages (from-to)2121-2129
Number of pages9
JournalJournal of Physiology
Volume593
Issue number9
DOIs
StatePublished - May 1 2015

ASJC Scopus subject areas

  • Physiology

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