Send to

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

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

Author information

Department of Pharmacology, Monash University, Clayton, VIC, 3800, Australia.


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.

[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Springer
Loading ...
Support Center