Inhibition of cystathionine‐gamma lyase dampens vasoconstriction in mouse and human intracerebral arterioles.

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
Read Online Read More Add to Saved list
  • Additional Information
    • Subject Terms:
      REVERSE transcriptase polymerase chain reaction; VASOCONSTRICTION; GUANYLATE cyclase; NITRIC-oxide synthases
    • Abstract:
      Aim: In extracerebral vascular beds cystathionine‐gamma lyase (CSE) activity plays a vasodilatory role but the role of this hydrogen sulfide (H2S) producing enzyme in the intracerebral arterioles remain poorly understood. We hypothesized a similar function in the intracerebral arterioles. Methods: Intracerebral arterioles were isolated from wild type C57BL/6J mouse (9–12 months old) brains and from human brain biopsies. The function (contractility and secondary dilatation) of the intracerebral arterioles was tested ex vivo by pressure myography using a perfusion set‐up. Reverse transcription polymerase chain reaction was used for detecting CSE expression. Results: CSE is expressed in human and mouse intracerebral arterioles. CSE inhibition with L‐propargylglycine (PAG) significantly dampened the K+‐induced vasoconstriction in intracerebral arterioles of both species (% of maximum contraction: in human control: 45.4 ± 2.7 versus PAG: 27 ± 5.2 and in mouse control: 50 ± 1.5 versus PAG: 33 ± 5.2) but did not affect the secondary dilatation. This effect of PAG was significantly reversed by the H2S donor sodium hydrosulfide (NaSH) in human (PAG + NaSH: 38.8 ± 7.2) and mouse (PAG + NaSH: 41.7 ± 3.1) arterioles, respectively. The endothelial NO synthase (eNOS) inhibitor, Nω‐Nitro‐l‐arginine methyl ester (L‐NAME), and the inhibitor of soluble guanylate cyclase (sGC), 1H‐[1,2,4]oxadiazolo[4,3‐a]quinoxalin‐1‐one (ODQ) reversed the effect of PAG on the K+‐induced vasoconstriction in the mouse arterioles and attenuated the K+‐induced secondary dilatation significantly. Conclusion: CSE contributes to the K+‐induced vasoconstriction via a mechanism involving H2S, eNOS, and sGC whereas the secondary dilatation is regulated by eNOS and sGC but not by CSE. [ABSTRACT FROM AUTHOR]
    • Abstract:
      Copyright of Acta Physiologica is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)