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

Maria Peleli, Kristina S. Lyngso, Frantz Rom Poulsen, Pernille B.L. Hansen, Andreas Papapetropoulos, Jane Stubbe

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


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.

Original languageEnglish (US)
Article numbere14021
JournalActa Physiologica
Issue number1
StatePublished - Sep 2023
Externally publishedYes


  • contractility
  • cystathionine-gamma lyase
  • endothelial NO synthase
  • hydrogen sulfide
  • intracerebral arterioles
  • soluble guanylate cyclase

ASJC Scopus subject areas

  • Physiology


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