Aldosterone, secreted by the glomerulosa cells of the adrenal cortex, stimulates the active uptake of sodium (Na+), and consequently water, from the glomerular filtrate in the distal tubules of the kidney. Aldosterone synthesis and release is controlled by the renin-angiotensin system.
Mechanism of Action
Aldosterone affects level of sodium
m reabsorption via the epithelial Na channels (ENaC) located at the distal nephron.
- Free aldosterone enters the tubule cells of the kidney and binds to the mineralocorticoid receptor (MR).
- This induces release of a heat shock protein (hsp), dimerization of two MRs and translocation to the nucleus.
- Where it binds to a glucocorticoid response element (GRE) on the DNA and, along with other transcription factors, initiates protein synthesis
- The aldosterone-induced proteins include factors that regulate the luminal Na+ channel and components of the Na+/K+ ATPase pump
Health and Diease
Imbalances in aldosterone can cause numerous health problems e.g. excessive aldosterone synthesis (hyperaldosteronism) and release may lead to hypertension. Hypertension is a risk factor in the development of diseases of the heart, vasculature and other organs such as the kidneys. Continued high blood pressure is cited as the commonest cause of stroke, which results from either blockage or, less commonly, haemorrhage of vulnerable blood vessels in the brain.
Hyperaldosteronism is the most likely common cause of mineralocorticoid hypertension and may occur in 0.01% to 0.03% of patients. Symptoms include sodium retention, heart rhythm irregularities and possibly muscle weakness as well as spontaneous or diuretic-induced hypokalaemia.
- ↑ Eaton DC,Malik B,Saxena NC, Al-Khalili OK, Yue. Mechanisms of aldosterone's action on epithelial Na+ transport.The Journal of membrane biology.2001;3:313-319