Schutzer William E, Mader Scott L
Portland VA Medical Center and Research Service-RD 26, Oregon Health and Science University School of Medicine, P.O. Box 1034, Portland, OR 97201, USA.
Int J Hypertens. 2012;2012:915057. doi: 10.1155/2012/915057. Epub 2011 Sep 22.
Hypertension, orthostatic hypotension, arterial insufficiency, and atherosclerosis are common disorders in the elderly that lead to significant morbidity and mortality. One common factor to these conditions is an age-related decline in vascular beta-adrenergic receptor-mediated function and subsequent cAMP generation. Presently, there is no single cellular factor that can explain this age-related decline, and thus, the primary cause of this homeostatic imbalance is yet to be identified. However, the etiology is clearly associated with an age-related change in the ability of beta-adrenergic receptor to respond to agonist at the cellular level in the vasculature. This paper will review what is presently understood regarding the molecular and biochemical basis of age-impaired beta-adrenergic receptor-mediated signaling. A fundamental understanding of why β-AR-mediated vasorelaxation is impaired with age will provide new insights and innovative strategies for the management of multiple clinical disorders.
高血压、体位性低血压、动脉供血不足和动脉粥样硬化是老年人常见的疾病,会导致显著的发病率和死亡率。这些病症的一个共同因素是血管β-肾上腺素能受体介导的功能随年龄增长而下降,以及随后环磷酸腺苷(cAMP)的生成减少。目前,没有单一的细胞因子能够解释这种与年龄相关的下降,因此,这种稳态失衡的主要原因尚未确定。然而,病因显然与β-肾上腺素能受体在血管系统细胞水平上对激动剂作出反应的能力随年龄增长而发生的变化有关。本文将综述目前对年龄相关的β-肾上腺素能受体介导信号受损的分子和生化基础的理解。对β-肾上腺素能受体介导的血管舒张功能为何随年龄增长而受损的基本理解,将为多种临床疾病的管理提供新的见解和创新策略。