See((Renin-angiotensin-aldosterone system (RAAS) ))
Aldosterone is the main mineralocorticoid steroid hormone produced by the zona glomerulosa of the adrenal cortex in the adrenal gland.
It is essential for sodium conservation in the kidney, salivary glands, sweat glands, and colon.
It has a central role in the homeostatic regulation of blood pressure, plasma sodium (Na+), and potassium (K+) levels.
It acts primarily by acting on the mineralocorticoid receptors in the distal tubules and collecting ducts of the nephron.
It influences the reabsorption of sodium and excretion of potassium from and into the tubular fluids, respectively, of the kidney, thereby indirectly influencing water retention or loss, blood pressure, and blood volume.
When it is dysregulated, aldosterone contributes to the development and progression of cardiovascular and kidney disease.
Aldosterone has exactly the opposite function of the atrial natriuretic hormone secreted by the heart.
Aldosterone is part of the renin–angiotensin–aldosterone system.
It’s plasma half-life of less than 20 minutes.
Drugs that interfere with the secretion or action of aldosterone are in use as antihypertensives: llisinopril, which lowers blood pressure by blocking the angiotensin-converting enzyme (ACE), leading to lower aldosterone secretion.
The net effect of these drugs is to reduce sodium and water retention but increase the retention of potassium. In other words, these drugs stimulate the excretion of sodium and water in urine, while they block the excretion of potassium.
Another example is spironolactone, a potassium-sparing diuretic of the steroidal spirolactone group, which interferes with the aldosterone receptor leading to lower blood pressure.
Corticosteroids are synthesized from cholesterol within the zona glomerulosa and zona fasciculata of adrenal cortex.
Most steroidogenic reactions are catalysed by enzymes of the cytochrome P450 family.
Aldosterone and corticosterone share the first part of their biosynthetic pathways.
Aldosterone synthesis is stimulated by several factors:
increase in the plasma concentration of angiotensin III, a metabolite of angiotensin II
increase in plasma angiotensin II, ACTH, or potassium levels, which are present in proportion to plasma sodium deficiencies.
The increased potassium level regulates aldosterone synthesis by depolarizing the cells in the zona glomerulosa, which opens the voltage-dependent calcium channels.
The level of angiotensin II is regulated by angiotensin I, which is in turn regulated by renin, a hormone secreted in the kidneys.
Serum potassium concentrations are the most potent stimulator of aldosterone secretion.
The ACTH stimulation test, is sometimes used to stimulate the production of aldosterone along with cortisol to determine whether primary or secondary adrenal insufficiency is present.
ACTH has only a minor role in regulating aldosterone production.
The stretch receptors located in the atria of the heart can detect decreased blood pressure, andvthe adrenal gland is stimulated by these stretch receptors to release aldosterone, which increases sodium reabsorption from the urine, sweat, and the gut.
This causes increased osmolarity in the extracellular fluid, returning blood pressure toward normal.
Adrenoglomerulotropin is a lipid factor, from pineal extracts whivh selectively stimulates secretion of aldosterone.
The secretion of aldosterone has a diurnal rhythm.
Aldosterone is the primary endogenou member of the class of mineralocorticoids.
Deoxycorticosterone is another important member of this class.
Aldosterone tends to promote Na+ and water retention, and lower plasma K+ concentration by the following mechanisms:
Acting on the mineralocorticoid receptors (MR) within the principal cells of the distal tubule and the collecting duct of the kidney nephron, it upregulates and activates the Na+/K+ pumps, which pumps three sodium ions out of the cell, into the interstitial fluid and two potassium ions into the cell from the interstitial fluid.
It creates a concentration gradient which results in reabsorption of sodium (Na+) ions and water into the blood, and secreting potassium (K+) ions into the urine.
Aldosterone upregulates epithelial sodium channels in the collecting duct and the colon, increasing apical membrane permeability for Na+ and thus absorption.
Chloride, is reabsorbed in conjunction with sodium cations to maintain the system’s electrochemical balance.
Aldosterone stimulates the secretion of K+ into the tubular lumen.
Aldosterone stimulates Na+ and water reabsorption from the gut, salivary and sweat glands in exchange for K+.
Aldosterone stimulates secretion of H+ via the intercalated cells of the cortical collecting tubules.
Aldosterone is responsible for the reabsorption of about 2% of filtered sodium in the kidneys, which is nearly equal to the entire sodium content in human blood under normal glomerular filtration rates. Mineralocorticoid receptors
Steroid receptors are intracellular.
The aldosterone mineralocorticoid receptor (MR) complex binds on the DNA to specific hormone response elements.
There are gene specific transcription genes crucial for transepithelial sodium transport: three subunits of the epithelial sodium channel (ENaC), the Na+/K+ pumps and their regulatory proteins serum and glucocorticoid-induced kinase, and channel-inducing factor, respectively.
The MR is stimulated by both aldosterone and cortisol, but a mechanism protects the body from excess aldosterone receptor stimulation by glucocorticoids: the enzyme 11 β-hydroxysteroid dehydrogenase (11β-HSD) co-localizes with intracellular adrenal steroid receptors and converts cortisol into cortisone, a relatively inactive metabolite with little affinity for the MR.
Liquorice, which contains glycyrrhetinic acid, can inhibit 11β-HSD and lead to a mineralocorticoid excess syndrome.
Angiotensin is involved in regulating aldosterone and is the primary regulator.
Angiotensin II acts synergistically with potassium, and the potassium feedback is virtually inoperative when no angiotensin II is present.
A small portion of the regulation resulting from angiotensin II must take place indirectly from decreased blood flow through the liver due to constriction of capillaries, as the blood flow decreases so does the destruction of aldosterone by liver enzymes.
Although sustained production of aldosterone requires persistent calcium entry through low-voltage-activated Ca2+ channels.
The amount of plasma renin secreted is an indirect function of the serum potassium as probably determined by sensors in the carotid artery.
Adrenocorticotropic hormone (ACTH), is a pituitary peptide with some stimulating effect on aldosterone, probably by stimulating the formation of deoxycorticosterone, a precursor of aldosterone.
Aldosterone is increased by blood loss, pregnancy, and possibly by physical exertion, endotoxin shock, and burns.
The aldosterone production is also affected to one extent or another by nervous control, integrating the inverse of carotid artery pressure, pain, posture, and probably the emotion of anxiety, fear, and hostility.
Pressure-sensitive baroreceptors are found in the vessel walls of nearly all large arteries in the thorax and neck.
Pressure-sensitive baroreceptors are particularly plentiful in the sinuses of the carotid arteries and in the arch of the aorta.
Pressure-sensitive baroreceptors are specialized receptors are sensitive to changes in mean arterial pressure.
An increase in sensed pressure results in an increased rate of firing by the baroreceptors and a negative feedback response, lowering systemic arterial pressure.
Aldosterone release causes sodium and water retention, which causes increased blood volume, and a subsequent increase in blood pressure, which is sensed by the baroreceptors.
These receptors also detect low blood pressure or low blood volume, causing aldosterone to be released, to maintain homeostasis, with sodium retention in the kidney, leading to water retention and increased blood volume.
Aldosterone levels vary as an inverse function of sodium intake as sensed via osmotic pressure.
Hyperaldosteronism is abnormally increased levels of aldosterone, while hypoaldosteronism is abnormally decreased levels of aldosterone.
Primary aldosteronism, also known as primary hyperaldosteronism, is characterized by the overproduction of aldosterone by the adrenal glands, when not a result of excessive renin secretion.
Primary aldosteronism leads to arterial hypertension associated with hypokalemia, usually a diagnostic clue.
Secondary hyperaldosteronism, on the other hand, is due to overactivity of the renin–angiotensin system.
Conn’s syndrome is primary hyperaldosteronism caused by an aldosterone-producing adenoma.
Depending on its cause hyperaldosteronism can be treated by surgery and/or medically, such as by aldosterone antagonists.
The ratio of renin to aldosterone is an effective screening test to screen for primary hyperaldosteronism related to adrenal adenomas.
It is the most sensitive serum blood test to differentiate primary from secondary causes of hyperaldosteronism.
An ACTH stimulation test for aldosterone can help in determining the cause of hypoaldosteronism, with a low aldosterone response indicating a primary hypoaldosteronism of the adrenals, while a large response indicating a secondary hypoaldosteronism.
The most common cause of this condition is Addison’s disease; it is typically treated by fludrocortisone, which has a much longer persistence in the bloodstream.