Regulation of vascular nitric oxide in vitro and in vivo; a new role for endogenous hydrogen sulphide?

Abstract

Background and Purpose: The aim of these experiments was to evaluate the significance of the chemical reaction between hydrogen sulphide (H 2 S) and nitric oxide (NO) for the control of vascular tone. Experimental Approach: The effect of sodium hydrosulphide (NaHS; H 2 S 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. Key Results: Mixing NaHS with NO donors inhibited the vasorelaxant effect of NO both in vitro and in vivo. Low concentrations of NaHS or H 2 S gas in solution reversed the relaxant effect of acetylcholine (ACh, 400 nM) and histamine (100 μM) 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 μM). In contrast, high concentrations of NaHS (200–1600 μM) relaxed aortic rings directly, an effect reduced by glibenclamide but unaffected by CuSO 4. Intravenous infusion of a low concentration of NaHS (10 μmol 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 and Implications: These results suggest that H 2 S 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 H 2 S in the vascular system is the regulation of the availability of NO. British Journal of Pharmacology (2006) 149, 625–634. doi:10.1038/sj.bjp.0706906