Abstract
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 (10−6 mol L−1) as well as soluble guanylyl cyclase (sGC) activation by runcaciguat (10−6 mol L−1) 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.
Highlights
IntroductionAged arteries contribute to cardiovascular disease [1,2]
The responses to PE, which were normalized to the respective KCl-induced contraction, were similar in both groups
We demonstrated that the age-dependent decline in the relaxing
Summary
Aged arteries contribute to cardiovascular disease [1,2]. Age-related decline in arterial function includes reduced vasorelaxation and increased vasoconstriction, which compromise organ perfusion and function. The decrease in endothelium-dependent vasodilatation that comes with age is not necessarily accompanied by structural changes in the arterial wall [3]. Disturbances in the generation or breakdown of endothelium-derived vasoactive 4.0/). What is typical is the attenuated response to vasodilators or to the blockade of the nitric oxide (NO) system, as shown by numerous studies in humans, rats, and mice [3,4,5,6,7]. The NO system, prostacyclin-derived metabolites, and the endothelium-derived hyperpolarizing factor (EDHF) are major components of the endothelial dilatory function
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
