Belmin J, Lévy B I, Michel J B
Hôpital de Gérontologie René Muret-Bigottini, Sevran, France.
Drugs Aging. 1994 Nov;5(5):391-400. doi: 10.2165/00002512-199405050-00007.
The renin-angiotensin-aldosterone system (RAAS) is one of the main systems involved in the regulation of blood pressure and sodium homeostasis. In animal experiments and in humans, the plasma renin activity and aldosterone levels are reduced with aging. The age-related differences in plasma renin activity and aldosterone are more pronounced in stimulated conditions (when sitting in an upright position, when salt intake is restricted and when plasma volume is depleted) than under basal conditions. Age-related alterations of the kidney (glomerulosclerosis, decreased number of functional nephrons) might account for the age-related differences in the active to inactive plasma renin ratio. In the same way, a diminished synthesis of angiotensinogen by the liver could contribute to the decrease in the activity of the RAAS in aging. This is partially compensated for by increases in the density of angiotensin II receptors reported in elderly patients. Furthermore, aging is associated with a reduced adrenal responsiveness to angiotensin II, contributing to lower production of aldosterone and alterations of sodium homeostasis. Estradiol and progesterone help stimulate the secretion of renin. Reduced levels of these hormones at menopause also lead to reduced plasma renin activity. In relation to these findings, several studies have shown that reductions in blood pressure, induced by short or long term treatment with angiotensin converting enzyme (ACE) inhibitors, were more pronounced in old than young hypertensive patients. An insertion/deletion polymorphism in the ACE gene has been described; the genotype deletion/deletion of this gene has been reported to be closely associated with longevity. This result was unexpected since the same deletion polymorphism was also shown to represent a potent risk factor for myocardial infarction.
肾素-血管紧张素-醛固酮系统（RAAS）是参与血压调节和钠稳态的主要系统之一。在动物实验和人体研究中，血浆肾素活性和醛固酮水平会随着年龄增长而降低。与年龄相关的血浆肾素活性和醛固酮差异在刺激条件下（如直立位、限盐及血浆容量减少时）比基础条件下更为明显。与年龄相关的肾脏改变（肾小球硬化、功能性肾单位数量减少）可能是血浆肾素活性与非活性肾素比值出现年龄相关差异的原因。同样，肝脏中血管紧张素原合成减少可能导致衰老过程中RAAS活性降低。老年患者中报道的血管紧张素II受体密度增加可部分补偿这一现象。此外，衰老与肾上腺对血管紧张素II的反应性降低有关，导致醛固酮生成减少和钠稳态改变。雌二醇和孕酮有助于刺激肾素分泌。绝经时这些激素水平降低也会导致血浆肾素活性降低。基于这些发现，多项研究表明，血管紧张素转换酶（ACE）抑制剂短期或长期治疗引起的血压降低在老年高血压患者中比年轻患者更为明显。已描述了ACE基因的插入/缺失多态性；据报道该基因的基因型缺失/缺失与长寿密切相关。这一结果出人意料，因为同样的缺失多态性也被证明是心肌梗死的一个强大危险因素。
