Age Impairs Soluble Guanylyl Cyclase Function in Mouse Mesenteric Arteries

Endothelial dysfunction (ED) comes with age, even without overt vessel damage such as that which occurs in atherosclerosis and diabetic vasculopathy. We hypothesized that aging would affect the downstream signalling of the endothelial nitric oxide (NO) system in the vascular smooth muscle (VSM). Wit...

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Autores principales:	Cheng Zhong, Minze Xu, Sengül Boral, Holger Summer, Falk-Bach Lichtenberger, Cem Erdoğan, Maik Gollasch, Stefan Golz, Pontus B. Persson, Johanna Schleifenbaum, Andreas Patzak, Pratik H. Khedkar
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	aging mesenteric artery nitric oxide soluble guanylyl cyclase soluble guanylyl cyclase activator Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/33b5db29157a4c4e88ce3322eb281f54
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spelling	oai:doaj.org-article:33b5db29157a4c4e88ce3322eb281f542021-11-11T16:53:06ZAge Impairs Soluble Guanylyl Cyclase Function in Mouse Mesenteric Arteries10.3390/ijms2221114121422-00671661-6596https://doaj.org/article/33b5db29157a4c4e88ce3322eb281f542021-10-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11412https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Endothelial dysfunction (ED) comes with age, even without overt vessel damage such as that which occurs in atherosclerosis and diabetic vasculopathy. We hypothesized that aging would affect the downstream signalling of the endothelial nitric oxide (NO) system in the vascular smooth muscle (VSM). With this in mind, resistance mesenteric arteries were isolated from 13-week (juvenile) and 40-week-old (aged) mice and tested under isometric conditions using wire myography. Acetylcholine (ACh)-induced relaxation was reduced in aged as compared to juvenile vessels. Pretreatment with L-NAME, which inhibits nitrix oxide synthases (NOS), decreased ACh-mediated vasorelaxation, whereby differences in vasorelaxation between groups disappeared. Endothelium-independent vasorelaxation by the NO donor sodium nitroprusside (SNP) was similar in both groups; however, SNP bolus application (10<sup>−6</sup> mol L<sup>−1</sup>) as well as soluble guanylyl cyclase (sGC) activation by runcaciguat (10<sup>−6</sup> mol L<sup>−1</sup>) caused faster responses in juvenile vessels. This was accompanied by higher cGMP concentrations and a stronger response to the PDE5 inhibitor sildenafil in juvenile vessels. Mesenteric arteries and aortas did not reveal apparent histological differences between groups (van Gieson staining). The mRNA expression of the α1 and α2 subunits of sGC was lower in aged animals, as was PDE5 mRNA expression. In conclusion, vasorelaxation is compromised at an early age in mice even in the absence of histopathological alterations. Vascular smooth muscle sGC is a key element in aged vessel dysfunction.Cheng ZhongMinze XuSengül BoralHolger SummerFalk-Bach LichtenbergerCem ErdoğanMaik GollaschStefan GolzPontus B. PerssonJohanna SchleifenbaumAndreas PatzakPratik H. KhedkarMDPI AGarticleagingmesenteric arterynitric oxidesoluble guanylyl cyclasesoluble guanylyl cyclase activatorBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11412, p 11412 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	aging mesenteric artery nitric oxide soluble guanylyl cyclase soluble guanylyl cyclase activator Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	aging mesenteric artery nitric oxide soluble guanylyl cyclase soluble guanylyl cyclase activator Biology (General) QH301-705.5 Chemistry QD1-999 Cheng Zhong Minze Xu Sengül Boral Holger Summer Falk-Bach Lichtenberger Cem Erdoğan Maik Gollasch Stefan Golz Pontus B. Persson Johanna Schleifenbaum Andreas Patzak Pratik H. Khedkar Age Impairs Soluble Guanylyl Cyclase Function in Mouse Mesenteric Arteries
description	Endothelial dysfunction (ED) comes with age, even without overt vessel damage such as that which occurs in atherosclerosis and diabetic vasculopathy. We hypothesized that aging would affect the downstream signalling of the endothelial nitric oxide (NO) system in the vascular smooth muscle (VSM). With this in mind, resistance mesenteric arteries were isolated from 13-week (juvenile) and 40-week-old (aged) mice and tested under isometric conditions using wire myography. Acetylcholine (ACh)-induced relaxation was reduced in aged as compared to juvenile vessels. Pretreatment with L-NAME, which inhibits nitrix oxide synthases (NOS), decreased ACh-mediated vasorelaxation, whereby differences in vasorelaxation between groups disappeared. Endothelium-independent vasorelaxation by the NO donor sodium nitroprusside (SNP) was similar in both groups; however, SNP bolus application (10<sup>−6</sup> mol L<sup>−1</sup>) as well as soluble guanylyl cyclase (sGC) activation by runcaciguat (10<sup>−6</sup> mol L<sup>−1</sup>) caused faster responses in juvenile vessels. This was accompanied by higher cGMP concentrations and a stronger response to the PDE5 inhibitor sildenafil in juvenile vessels. Mesenteric arteries and aortas did not reveal apparent histological differences between groups (van Gieson staining). The mRNA expression of the α1 and α2 subunits of sGC was lower in aged animals, as was PDE5 mRNA expression. In conclusion, vasorelaxation is compromised at an early age in mice even in the absence of histopathological alterations. Vascular smooth muscle sGC is a key element in aged vessel dysfunction.
format	article
author	Cheng Zhong Minze Xu Sengül Boral Holger Summer Falk-Bach Lichtenberger Cem Erdoğan Maik Gollasch Stefan Golz Pontus B. Persson Johanna Schleifenbaum Andreas Patzak Pratik H. Khedkar
author_facet	Cheng Zhong Minze Xu Sengül Boral Holger Summer Falk-Bach Lichtenberger Cem Erdoğan Maik Gollasch Stefan Golz Pontus B. Persson Johanna Schleifenbaum Andreas Patzak Pratik H. Khedkar
author_sort	Cheng Zhong
title	Age Impairs Soluble Guanylyl Cyclase Function in Mouse Mesenteric Arteries
title_short	Age Impairs Soluble Guanylyl Cyclase Function in Mouse Mesenteric Arteries
title_full	Age Impairs Soluble Guanylyl Cyclase Function in Mouse Mesenteric Arteries
title_fullStr	Age Impairs Soluble Guanylyl Cyclase Function in Mouse Mesenteric Arteries
title_full_unstemmed	Age Impairs Soluble Guanylyl Cyclase Function in Mouse Mesenteric Arteries
title_sort	age impairs soluble guanylyl cyclase function in mouse mesenteric arteries
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/33b5db29157a4c4e88ce3322eb281f54
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Age Impairs Soluble Guanylyl Cyclase Function in Mouse Mesenteric Arteries

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