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Evidence for a functional vasodilatatory role for hydrogen sulphide in the human cutaneous microvasculature
Author(s) -
Kutz Jessica L.,
Greaney Jody L.,
Santhanam Lakshmi,
Alexander Lacy M.
Publication year - 2015
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jp270054
Subject(s) - vasodilation , nitric oxide , chemistry , cystathionine beta synthase , microcirculation , vascular smooth muscle , pharmacology , biochemistry , enzyme , medicine , cysteine , organic chemistry , smooth muscle
Key points Hydrogen sulphide (H 2 S) is vasoprotective, attenuates inflammation and modulates blood pressure in animal models; however, its specific mechanistic role in the human vasculature remains unclear. In the present study, we report the novel finding that the enzymes responsible for endogenous H 2 S production, cystathionine‐γ‐lyase and 3‐mercaptopyruvate sulphurtransferase, are expressed in the human cutaneous circulation. Functionally, we show that H 2 S‐induced cutaneous vasodilatation is mediated, in part, by tetraethylammonium‐sensitive calcium‐dependent potassium channels and not by ATP‐sensitive potassium channels. In addition, nitric oxide and cyclo‐oxygenase‐derived byproducts are required for full expression of exogenous H 2 S‐mediated cutaneous vasodilatation. Future investigations of the potential role for H 2 S with respect to modulating vascular function in humans may have important clinical implications for understanding the mechanisms underlying vascular dysfunction characteristic of multiple cardiovascular pathologies.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 (H 2 S), and to functionally examine the mechanisms of H 2 S‐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 m m ) of sodium sulphide (Na 2 S) and sodium hydrogen sulphide (NaHS). To define the mechanisms mediating H 2 S‐induced vasodilatation, microdialysis fibres were perfused with Ringer solution (control), a ATP‐sensitive potassium channel (K ATP ) inhibitor, an intermediate calcium‐dependent potassium channel (K Ca ) inhibitor, a non‐specific K Ca channel inhibitor or triple blockade. To determine the interaction of H 2 S‐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 Na 2 S. CSE and 3‐MST were expressed in all skin samples. Na 2 S and NaHS elicited dose‐dependent vasodilatation. Non‐specific K Ca channel inhibition and triple blockade blunted Na 2 S‐induced vasodilatation ( P < 0.05), whereas K ATP and intermediate K Ca channel inhibition had no effect ( P > 0.05). Separate and combined inhibition of NO and COX attenuated H 2 S‐induced vasodilatation (all P < 0.05). CSE and 3‐MST are expressed in the human microvasculature. Exogenous H 2 S elicits cutaneous vasodilatation mediated by K Ca channels and has a functional interaction with both NO and COX vasodilatatory signalling pathways.