Mechanism of vasorelaxation and role of endogenous hydrogen sulfide production in mouse aorta

Naunyn Schmiedebergs Arch Pharmacol. 2011 Apr;383(4):403-13. doi: 10.1007/s00210-011-0608-z. Epub 2011 Feb 19.


This study aimed to elucidate the molecular mechanism of H(2)S-induced vasorelaxation. Vasorelaxation responses to the H(2)S donor NaHS and the H(2)S precursor L: -cysteine were examined by measuring isometric tone of mouse aortic rings in a small vessel myograph. H(2)S concentrations in Krebs' solution were determined with a polarographic sensor. H(2)S expression was examined by Western blot, and H(2)S production from CSE was assayed using a spectroscopic method. In pre-constricted mouse aorta, NaHS (1 μM-3 mM) elicited vasorelaxation of 95 ± 7%, EC(50) 189 ± 69 μM. This response was unaffected by removal of the endothelium. Maximum vasorelaxation was significantly attenuated by global blockade of K(+) channels (50 mM K(+)) and the K(ATP) channel blocker glibenclamide (10 μM) alone (P < 0.01, ANOVA). Specific inhibition of K(Ca), K(IR), or K(V) channels elicited a significant shift to the right in the concentration-response curve to NaHS (P < 0.01, ANOVA) without affecting maximum relaxation. NaHS-mediated vasorelaxation was inhibited by the Cl(-) channel inhibitor DIDS (1 mM, P < 0.05, t test), and NaHS caused a significant concentration-dependent inhibition of voltage-gated Ca(2+) channels (P < 0.001, two-way ANOVA). The H(2)S-producing enzyme cystathionine-γ-lyase (CSE) was expressed in mouse aorta and had activity of 7 ± 3 μmol H(2)S/g/min. L: -cysteine (1 μM-3 mM) elicited a CSE-dependent vasorelaxation of mouse aorta with intact endothelium (20 ± 7%), but not when the endothelium was removed. CSE inhibitors DL: -propargylglycine (20 mM) and β-cyanoalanine (1 mM) caused concentration-dependent contraction of mouse aorta. In mouse aorta, H(2)S elicits endothelium-independent vasorelaxation involving several different ion channels and seems to converge at the vascular smooth muscle cell voltage-gated Ca(2+) channel. The L: -cysteine-CSE-H(2)S pathway contributes to vasorelaxation and appears to modulate basal vessel tone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aorta / drug effects
  • Aorta / metabolism*
  • Blotting, Western
  • Calcium Channels / metabolism
  • Cystathionine gamma-Lyase / metabolism
  • Cysteine / metabolism
  • Dose-Response Relationship, Drug
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / metabolism
  • Hydrogen Sulfide / metabolism*
  • Ion Channels / drug effects
  • Ion Channels / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / metabolism
  • Myography
  • Sulfides / administration & dosage
  • Sulfides / pharmacology*
  • Vasodilation / drug effects*


  • Calcium Channels
  • Ion Channels
  • Sulfides
  • Cystathionine gamma-Lyase
  • sodium bisulfide
  • Cysteine
  • Hydrogen Sulfide