Changes in Cerebral Arteries and Parenchymal Arterioles With Aging: Role of Rho Kinase 2 and Impact of Genetic Background

• Published in: Hypertension (Dallas, Tex. 1979) Tex. 1979), 2018-05, Vol.71 (5), p.921-927
• Main Authors: De Silva, T Michael, Modrick, Mary L, Dabertrand, Fabrice, Faraci, Frank M
• Format: Article
• Language: English
• Subjects: Aging - genetics; Analysis of Variance; Animals; Arterioles - metabolism; Cerebral Arteries - metabolism; Endothelium, Vascular - metabolism; Genetic Background; Male; Mice; Mice, Inbred C57BL; Muscle, Smooth, Vascular - metabolism; Nitric Oxide - metabolism; rho-Associated Kinases - genetics; Sensitivity and Specificity; Vascular Diseases - genetics; Vascular Diseases - physiopathology
• ISSN: 0194-911X; 1524-4563
• DOI: 10.1161/HYPERTENSIONAHA.118.10865

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 ROCK (Rho kinase) plays an important role. In C57BL/6 mice, baseline diameters of isolated pressurized parenchymal arterioles were similar in adult (4–5 month) and old mice (22±1 month; ≈15±1 µm). Endothelium-dependent dilation was impaired in old mice compared with adults in a pathway-specific manner. Vasodilation to NS-309 (which activates small- and intermediate-conductance Ca activated K channels in endothelial cells) was intact while endothelial nitric oxide synthase–mediated vasodilation was reduced by ≥60%, depending on the concentration (P