Journal article
Changes in Cerebral Arteries and Parenchymal Arterioles with Aging: Role of ROCK2 and Impact of Genetic Background
Hypertension (Dallas, Tex. 1979), Vol.71(5), pp.921-927
03/12/2018
DOI: 10.1161/HYPERTENSIONAHA.118.10865
PMCID: PMC5897142
PMID: 29531174
Abstract
Vascular aging fundamentally contributes to large and small vessel disease. Despite the importance of such changes for brain function, mechanisms that mediate such changes are poorly defined. We explored mechanisms that underlie changes with age, testing the hypothesis that Rho kinase (ROCK) plays an important role. In C57BL/6 mice, baseline diameter of isolated pressurized parenchymal arterioles were similar in adult (4–5 month) and old mice (22±1 month)(~15±1 microns). Endothelium-dependent dilation was impaired in old mice compared to adults in a pathway-specific manner. Vasodilation to NS-309 (which activates small- and intermediate-conductance Ca
2+
activated K
+
channels in endothelial cells) was intact, while endothelial nitric oxide (NO) synthase (eNOS)-mediated vasodilation was reduced by 60% or more, depending on the concentration (p<0.05). A similar reduction was present in basilar arteries. Inhibiting both ROCK isoforms with Y-27632 restored the majority of endothelial function in old mice. Because genetic background is a determinant of vascular disease, we performed similar studies using FVB/N mice. Endothelial dysfunction was seen with aging in both FVB/N and C57BL/6 mice, although the magnitude was increased almost 2-fold in the latter strain (p<0.05). In both strains of mice, age-induced endothelial dysfunction was reversed by inhibition of ROCK2 with SLX-2119. Thus, aging impairs endothelial function in both cerebral arteries and parenchymal arterioles, predominantly via effects on eNOS-dependent regulation of vascular tone. The magnitude of these changes was influenced by genetic background and mediated by ROCK2.
Details
- Title: Subtitle
- Changes in Cerebral Arteries and Parenchymal Arterioles with Aging: Role of ROCK2 and Impact of Genetic Background
- Creators
- T. Michael De Silva - University of VermontMary L. Modrick - University of VermontFabrice Dabertrand - University of VermontFrank M. Faraci - University of Vermont
- Resource Type
- Journal article
- Publication Details
- Hypertension (Dallas, Tex. 1979), Vol.71(5), pp.921-927
- DOI
- 10.1161/HYPERTENSIONAHA.118.10865
- PMID
- 29531174
- PMCID
- PMC5897142
- NLM abbreviation
- Hypertension
- ISSN
- 0194-911X
- eISSN
- 1524-4563
- Language
- English
- Date published
- 03/12/2018
- Academic Unit
- Cardiovascular Medicine; Neuroscience and Pharmacology; Internal Medicine
- Record Identifier
- 9984303742202771
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