Heterogeneous effect of aging on vasorelaxation responses in large and small arteries

Luttrell, Meredith J.; Kim, Hyo-Seon; Shin, Song Yi; Holly, Dylan; Massett, Michael P.; Woodman, Christopher R.

doi:10.14814/phy2.14341

Cited by 14 publications

(20 citation statements)

References 38 publications

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“…Another study on vascular tissue from diabetic patients reported a development of a hypercontractile phenotype of the vessels from femoral region used as a vascular conduit in coronary artery bypass grafting, 14 as authors reported that the underlying mechanism relates to a diminution of the activity of the enzyme myosin light chain phosphatase (MLCP). A causal link between ageing, impaired vasodilator responses and endothelial dysfunction in large conducting vessels has been reported by others 15 . Altogether, these data support the view that ageing affects all components of vascular regulation, i.e., neuronal, endothelial and smooth muscle cells, leading to development of an abnormal vascular phenotype, often associated with hypercontractility.…”

Section: Introductionsupporting

confidence: 83%

Senescent murine femoral arteries undergo vascular remodelling associated with accelerated stress‐induced contractility and reactivity to nitric oxide

Lubomirov

Jänsch

Papadopoulos

et al. 2021

Basic Clin Pharma Tox

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This work explored the mechanism of augmented stress‐induced vascular reactivity of senescent murine femoral arteries (FAs). Mechanical and pharmacological reactivity of young (12–25 weeks, y‐FA) and senescent (>104 weeks, s‐FAs) femoral arteries was measured by wire myography. Expression and protein phosphorylation of selected regulatory proteins were studied by western blotting. Expression ratio of the Exon24 in/out splice isoforms of the regulatory subunit of myosin phosphatase, MYPT1 (MYPT1‐Exon24 in/out), was determined by polymerase chain reaction (PCR). While the resting length–tension relationship showed no alteration, the stretch‐induced‐tone increased to 8.3 ± 0.9 mN in s‐FA versus only 4.6 ± 0.3 mN in y‐FAs. Under basal conditions, phosphorylation of the regulatory light chain of myosin at S19 was 19.2 ± 5.8% in y‐FA versus 49.2 ± 12.6% in s‐FA. Inhibition of endogenous NO release raised tone additionally to 10.4 ± 1.2 mN in s‐FA, whereas this treatment had a negligible effect in y‐FAs (4.8 ± 0.3 mN). In s‐FAs, reactivity to NO donor was augmented (pD2 = −4.5 ± 0.3 in y‐FA vs. ‐5.2 ± 0.1 in senescent). Accordingly, in s‐FAs, MYPT1‐Exon24‐out‐mRNA, which is responsible for expression of the more sensitive to protein‐kinase G, leucine‐zipper‐positive MYPT1 isoform, was increased. The present work provides evidence that senescent murine s‐FA undergoes vascular remodelling associated with increases in stretch‐activated contractility and sensitivity to NO/cGMP/PKG system.

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Section: Introductionsupporting

confidence: 83%

Senescent murine femoral arteries undergo vascular remodelling associated with accelerated stress‐induced contractility and reactivity to nitric oxide

Lubomirov

Jänsch

Papadopoulos

et al. 2021

Basic Clin Pharma Tox

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“…The observation corresponds with the literature and reflects the comparatively lower contribution of NO from nNOS to vasorelaxation [ 44 , 45 ]. Studies on the effect of age on eNOS expression do not provide a uniform picture and report either unaltered or decreased eNOS mRNA and protein expressions [ 46 , 47 , 48 , 49 , 50 ]. Other studies have also found increased eNOS mRNA expression [ 50 , 51 ].…”

Section: Discussionmentioning

confidence: 99%

Age Impairs Soluble Guanylyl Cyclase Function in Mouse Mesenteric Arteries

Zhong

Boral

et al. 2021

IJMS

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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.

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“…The anatomic variation in the influence of age on endothelial function may be related to increased pulse pressure and reduced eNOS mRNA expression in the aorta (Barton et al, 1997). In rats, acetylcholine-induced vasorelaxation is impaired in large conduit arteries (abdominal aorta and iliac arteries) but not in smaller conduit (femoral arteries) or resistance arteries (Luttrell et al, 2020).…”

Section: Endothelial Dysfunctionmentioning

confidence: 99%

Vascular Stiffness in Aging and Disease

et al. 2021

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The goal of this review is to provide further understanding of increased vascular stiffness with aging, and how it contributes to the adverse effects of major human diseases. Differences in stiffness down the aortic tree are discussed, a topic requiring further research, because most prior work only examined one location in the aorta. It is also important to understand the divergent effects of increased aortic stiffness between males and females, principally due to the protective role of female sex hormones prior to menopause. Another goal is to review human and non-human primate data and contrast them with data in rodents. This is particularly important for understanding sex differences in vascular stiffness with aging as well as the changes in vascular stiffness before and after menopause in females, as this is controversial. This area of research necessitates studies in humans and non-human primates, since rodents do not go through menopause. The most important mechanism studied as a cause of age-related increases in vascular stiffness is an alteration in the vascular extracellular matrix resulting from an increase in collagen and decrease in elastin. However, there are other mechanisms mediating increased vascular stiffness, such as collagen and elastin disarray, calcium deposition, endothelial dysfunction, and the number of vascular smooth muscle cells (VSMCs). Populations with increased longevity, who live in areas called “Blue Zones,” are also discussed as they provide additional insights into mechanisms that protect against age-related increases in vascular stiffness. Such increases in vascular stiffness are important in mediating the adverse effects of major cardiovascular diseases, including atherosclerosis, hypertension and diabetes, but require further research into their mechanisms and treatment.

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Heterogeneous effect of aging on vasorelaxation responses in large and small arteries

Cited by 14 publications

References 38 publications

Senescent murine femoral arteries undergo vascular remodelling associated with accelerated stress‐induced contractility and reactivity to nitric oxide

Senescent murine femoral arteries undergo vascular remodelling associated with accelerated stress‐induced contractility and reactivity to nitric oxide

Age Impairs Soluble Guanylyl Cyclase Function in Mouse Mesenteric Arteries

Vascular Stiffness in Aging and Disease

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