Inhibition of cystathionine‐gamma lyase dampens vasoconstriction in mouse and human intracerebral arterioles
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| Názov: | Inhibition of cystathionine‐gamma lyase dampens vasoconstriction in mouse and human intracerebral arterioles |
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| Autori: | Maria Peleli, Kristina S. Lyngso, Frantz Rom Poulsen, Pernille B. L. Hansen, Andreas Papapetropoulos, Jane Stubbe |
| Zdroj: | Acta Physiologica. 239 |
| Informácie o vydavateľovi: | Wiley, 2023. |
| Rok vydania: | 2023 |
| Predmety: | cystathionine-gamma lyase, soluble guanylate cyclase, Enzyme Inhibitors/pharmacology, Arterioles/drug effects, Hydrogen Sulfide/metabolism, hydrogen sulfide, Cystathionine gamma-Lyase, Pharmacology and Toxicology, Farmakologi och toxikologi, Inbred C57BL, contractility, Mice, Inbred C57BL, Mice, Arterioles, Vasoconstriction, Cystathionine gamma-Lyase/antagonists & inhibitors, endothelial NO synthase, Animals, Humans, Hydrogen Sulfide, Enzyme Inhibitors, intracerebral arterioles |
| Popis: | AimIn 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.MethodsIntracerebral 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.ResultsCSE 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.ConclusionCSE 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. |
| Druh dokumentu: | Article |
| Popis súboru: | application/pdf |
| Jazyk: | English |
| ISSN: | 1748-1716 1748-1708 |
| DOI: | 10.1111/apha.14021 |
| Prístupová URL adresa: | https://pubmed.ncbi.nlm.nih.gov/37555636 https://pergamos.lib.uoa.gr/uoa/dl/object/3490125 http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-531647 |
| Rights: | CC BY |
| Prístupové číslo: | edsair.doi.dedup.....2d0053bef1493bb44e93bc2474ae7dad |
| Databáza: | OpenAIRE |
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Nájsť tento článok vo Web of Science | Abstrakt: | AimIn 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.MethodsIntracerebral 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.ResultsCSE 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.ConclusionCSE 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. |
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| ISSN: | 17481716 17481708 |
| DOI: | 10.1111/apha.14021 |