Scarpace P J, Tumer N, Mader S L
Geriatric Research, Education and Clinical Center, Department of Veterans Affairs Medical Center, Gainesville, Florida.
Drugs Aging. 1991 Mar;1(2):116-29. doi: 10.2165/00002512-199101020-00004.
Catecholamines have an important endocrine and neuroendocrine role in mediating a variety of autonomic functions. One consequence of normal aging, in particular in the cardiovascular system, is a decline in beta-adrenergic function associated with an alteration in responsiveness to beta-adrenergic therapy. The intrinsic ability for muscle contractility or relaxation is maintained with age and there appears to be an alteration in the process linking the receptor with the contractile or relaxation mechanisms. In rats, beta-adrenergic receptor density decreases with age in adipose tissues and most brain areas, is unchanged in lymphocytes, heart and lung, and increases in the liver. In humans, there are no receptor changes with age in either lymphocytes or brain. In contrast, the number of high-affinity receptors (or coupled receptors) decreases with age in most tissues. In addition, there is a decrease in membrane adenylate cyclase activity or cellular production of cyclic adenosine monophosphate (adenosine 3',5'-cyclic phosphate; cAMP). Plasma noradrenaline (norepinephrine) concentration increases with age. The reduced receptor number in some tissues (down-regulation), the reduced high-affinity receptors and the reduced hormone-stimulated adenylate cyclase activity with age suggests receptor desensitisation to increased plasma noradrenaline concentration. The inability of older animals to desensitise to beta-adrenergic agonists further supports this hypothesis. However, there is an additional post-receptor reduction in catalytic unit activity with age independent of desensitisation. Medications directed at the beta-adrenergic system are commonly used in the elderly. Many of the data on the impact of age on clinical responses are conflicting or unavailable. Concomitant disease, functional status, nutritional state and polypharmacy may play an even greater role than age. However, the available data can be used to guide the selection of therapy, anticipate side effects, and predict potential interactions with other medications and diseases.
儿茶酚胺在介导多种自主功能方面具有重要的内分泌和神经内分泌作用。正常衰老的一个后果，尤其是在心血管系统中，是β-肾上腺素能功能下降，这与对β-肾上腺素能治疗的反应性改变有关。肌肉收缩或舒张的内在能力随年龄保持不变，并且在将受体与收缩或舒张机制联系起来的过程中似乎存在改变。在大鼠中，脂肪组织和大多数脑区的β-肾上腺素能受体密度随年龄降低，淋巴细胞、心脏和肺中的受体密度不变，而肝脏中的受体密度增加。在人类中，淋巴细胞或大脑中的受体数量不会随年龄变化。相比之下，大多数组织中高亲和力受体（或偶联受体）的数量随年龄减少。此外，膜腺苷酸环化酶活性或环磷酸腺苷（腺苷3'，5'-环磷酸；cAMP）的细胞产生减少。血浆去甲肾上腺素浓度随年龄增加。某些组织中受体数量减少（下调）、高亲和力受体减少以及激素刺激的腺苷酸环化酶活性随年龄降低表明受体对血浆去甲肾上腺素浓度升高脱敏。老年动物对β-肾上腺素能激动剂脱敏的能力不足进一步支持了这一假设。然而，随着年龄的增长，受体后催化单位活性还有额外的降低，这与脱敏无关。针对β-肾上腺素能系统的药物常用于老年人。许多关于年龄对临床反应影响的数据相互矛盾或无法获得。合并症、功能状态、营养状况和多重用药可能比年龄起更大的作用。然而，现有数据可用于指导治疗选择、预测副作用以及预测与其他药物和疾病的潜在相互作用。
