Tümer Nihal, Toklu Hale Z, Muller-Delp Judy M, Oktay Sehkar, Ghosh Payal, Strang Kevin, Delp Michael D, Scarpace Philip J
Geriatric Research, Education, and Clinical Center, North Florida/South Georgia Veterans Health System, Gainesville, Florida, USA Department of Pharmacology and Therapeutics, University of Florida, Gainesville, Florida, USA.
Department of Physiology and Functional Genomics, University of Florida, Gainesville, Florida, USA.
Physiol Rep. 2014 Jun 6;2(6). doi: 10.14814/phy2.12031. Print 2014 Jun 1.
Aging leads to progressive pathophysiological changes in blood vessels of the brain and periphery. The aim of this study was to evaluate the effects of aging on cerebral vascular function and structure. Basilar arteries were isolated from male Fischer 344 cross Brown Norway (F344xBN) rats at 3, 8, and 24 months of age. The basilar arteries were cannulated in the pressurized system (90 cm H2O). Contractile responses to KCl (30-120 mmol/L) and endothelin-1 (10(-11)-10(-7) mol/L) were evaluated. Responses to acetylcholine (ACh) (10(-10)-10(-4) mol/L), diethylamine (DEA)-NONO-ate (10(-10)-10(-4) mol/L), and papaverin (10(-10)-10(-4) mol/L) were assessed to determine both endothelium-dependent and endothelium-independent responsiveness. Advanced aging (24 months) decreased responses of the basilar artery to both the contractile and relaxing agents; whereas, DEA-induced dilation was significantly higher in the 8-month-old group compared with the younger and older groups. The arterial wall-to-lumen ratio was significantly increased in 24-month-old rats. Smooth muscle cell count was also decreased in old rats. These findings indicate that aging produces dysfunction of both the endothelium and the vascular smooth muscle in the basilar artery. Aging also alters wall structure of the basilar artery, possibly through decreases in smooth muscle cell number and concomitant hypertrophy.
衰老会导致大脑和外周血管发生渐进性的病理生理变化。本研究的目的是评估衰老对脑血管功能和结构的影响。从3个月、8个月和24个月大的雄性Fischer 344与棕色挪威大鼠（F344xBN）杂交后代中分离出基底动脉。将基底动脉插管于加压系统（90 cm H2O）中。评估对氯化钾（30 - 120 mmol/L）和内皮素-1（10(-11) - 10(-7) mol/L）的收缩反应。评估对乙酰胆碱（ACh）（10(-10) - 10(-4) mol/L）、二乙胺（DEA）- NONO - 酯（10(-10) - 10(-4) mol/L）和罂粟碱（10(-10) - 10(-4) mol/L）的反应，以确定内皮依赖性和非内皮依赖性反应性。衰老（24个月）会降低基底动脉对收缩剂和舒张剂的反应；然而，与年轻组和老年组相比，8个月大的组中DEA诱导的舒张作用显著更高。24个月大的大鼠动脉壁与管腔的比例显著增加。老年大鼠的平滑肌细胞数量也减少。这些发现表明，衰老会导致基底动脉的内皮和血管平滑肌功能障碍。衰老还会改变基底动脉的壁结构，可能是通过平滑肌细胞数量的减少和随之而来的肥大。
