Changes in the Renin-Angiotensin-Aldosterone Axis in Later Life

Abstract

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.

Screening for primary aldosteronism in an argentinian population: a multicenter prospective study

“…This is consistent with findings reported by other authors evaluating normotensive subjects (30) and hypertensive patients (31), but it differs from other author's reports (32), where both ALD and PRA were found to decrease with age.…”

Spontaneous Resolution of Idiopathic Aldosteronism After Long-Term Treatment With Potassium Canrenoate

“…Furthermore, aging is associated with a reduced adrenal responsiveness to angiotensin II, contributing to lower production of aldosterone and imbalance of sodium homeostasis. 3 We hypothesize that prolonged treatment with KC can normalize the response of glomerulosa to angiotensin II and reverse the clinical picture in some cases of IPA. We did not find any evident cardiovascular alteration in our subjects, even after long-term withdrawal from the therapy, in agreement with a positive effect of aldosterone-receptor blockers to prevent further worsening of this aspect of the disease.…”

Angiotensin II in the Elderly

“…23 Thus, the current data extend this earlier work in the forearm, demonstrating for the first time a significant increase in AT 1 receptor sensitivity in the leg vasculature of healthy elderly individuals at rest. Although the mechanism for increased AT 1 responsiveness may be as simple as receptor upregulation in response to reduced substrate, 24 this pathway may become an increasingly important regulator of peripheral hemodynamics with advancing age. Recent studies have identified a reduction in postjunctional ␣-adrenergic receptor sensitivity in both the arm 25 and leg of older individuals, 26 yet ␣-adrenergic blockade in this population does not completely restore hemodynamics to that of the young.…”