Regulation of vascular nitric oxide in vitro and in vivo; a new role for endogenous hydrogen sulphide?
OBJECTIVE
The aim of these experiments was to evaluate the significance of the chemical reaction between hydrogen sulphide (H2S) and nitric oxide (NO) for the control of vascular tone.


METHODS
The effect of sodium hydrosulphide (NaHS; H2S donor) and a range of NO donors, such as sodium nitroprusside (SNP), either alone or together, was determined using phenylephrine (PE)-precontracted rat aortic rings and on the blood pressure of anaesthetised rats.


RESULTS
Mixing NaHS with NO donors inhibited the vasorelaxant effect of NO both in vitro and in vivo. Low concentrations of NaHS or H2S gas in solution reversed the relaxant effect of acetylcholine (ACh, 400 nM) and histamine (100 microM) but not isoprenaline (400 nM). The effect of NaHS on the ACh response was antagonized by CuSO(4) (200 nM) but was unaffected by glibenclamide (10 microM). In contrast, high concentrations of NaHS (200-1600 microM) relaxed aortic rings directly, an effect reduced by glibenclamide but unaffected by CuSO4. Intravenous infusion of a low concentration of NaHS (10 micromol kg(-1) min(-1)) into the anaesthetized rat significantly increased mean arterial blood pressure. L-NAME (25 mg kg(-1), i.v.) pretreatment reduced this effect.


CONCLUSIONS
These results suggest that H2S and NO react together to form a molecule (possibly a nitrosothiol) which exhibits little or no vasorelaxant activity either in vitro or in vivo. We propose that a crucial, and hitherto unappreciated, role of H2S in the vascular system is the regulation of the availability of NO.
Ali
M Y
MY
Department of Pharmacology, Cardiovascular Biology Research Group, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Ping
C Y
CY
Mok
Y-Yp
YY
Ling
L
L
Whiteman
M
M
Bhatia
M
M
Moore
P K
PK
D000818:Animals; D001011:Aorta / Q000378:metabolism* / Q000502:physiology; D001794:Blood Pressure; D006862:Hydrogen Sulfide / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D020030:Nitric Oxide Donors; D009599:Nitroprusside; D009569:Nitric Oxide; D006862:Hydrogen Sulfide