Abstract
Abstract WP426: Rock2-mediated Cerebrovascular Dysfunction During Aging
Stroke (1970), Vol.48(suppl_1)
02/2017
DOI: 10.1161/str.48.suppl_1.wp426
Abstract
The pathophysiological changes that occur during vascular aging fundamentally contribute to large and small vessel disease. Despite the importance of such changes for stroke and cognitive dysfunction, mechanisms that underlie vascular aging remain very poorly defined. As a result, no specific therapies exist at present. Because loss of endothelial health is a cornerstone event in the progression of vascular disease, we explored mechanisms that underlie vascular changes with aging, testing the hypothesis that Rho kinase (ROCK) plays an important role. In C57Bl/6J mice, baseline diameter of isolated parenchymal arterioles were similar in both adult (4-5 mo of age) and old mice (22±1 mo) (15±1 microns). Endothelium-dependent dilation was significantly impaired in old mice compared to adult controls, but in a pathway-specific manner. Vasodilation mediated by endothelium-dependent hyperpolarization was intact while eNOS-mediated responses were reduced by approximately 50% (P<0.05). A similar reduction in eNOS-dependent endothelial function was present in isolated basilar arteries. Inhibition of both ROCK1 and ROCK2 isoforms with Y-27632 or ROCK2 only with SLX-2119, restored endothelial function in old mice. An inhibitor of NO synthase reversed this protective effect, demonstrating that inhibition of ROCK2 restored NO-mediated signaling during aging. Because genetic background is a determinant of vascular disease, we performed similar studies using FVB/NJ mice. Like the C57Bl/6J mice, FVB/NJ mice exhibited endothelial dysfunction with aging that was reversed by inhibition of ROCK2. Thus, aging impairs endothelial function in both cerebral arteries and the smallest parenchymal arterioles via effects on select pathways. Vascular aging and the underlying mechanisms are not limited to one genetic background. These studies provide the first evidence that ROCK2 is a key contributor to cerebrovascular dysfunction with aging.
Details
- Title: Subtitle
- Abstract WP426: Rock2-mediated Cerebrovascular Dysfunction During Aging
- Creators
- Travice M De Silva - University of IowaMary Modrick - University of IowaFrank M Faraci - University of Iowa
- Resource Type
- Abstract
- Publication Details
- Stroke (1970), Vol.48(suppl_1)
- DOI
- 10.1161/str.48.suppl_1.wp426
- ISSN
- 0039-2499
- eISSN
- 1524-4628
- Language
- English
- Date published
- 02/2017
- Academic Unit
- Neuroscience and Pharmacology; Cardiovascular Medicine; Internal Medicine
- Record Identifier
- 9984303995102771
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