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What’s Aldosterone?
Discovery1
Italian anatomist Bartolomeo Eustacchio recorded the earliest known depiction of the adrenal gland in 1563. Studies on the adrenal cortex picked up after 1849, when Thomas Addison (not the lightbulb guy) published a discussion of a fatal syndrome that could result from its destruction. While many glucocorticoids were isolated by the 1930s, research on mineralocorticoids was slower.
Globally, several teams of researchers persisted in trying to isolate a hypostulated mineralocorticoid, which they called “electrocortin.” By 1948, one team had shown that electrocortin was produced and secreted from the zona glomerulosa of the adrenal cortex in response to a reduced sodium diet.

In 1953, English scientists Simpson and Tate developed a bioassay that allowed isolation of electrocortin from the adrenal glands of a cow. In the following months, the structure of aldosterone was finally determined, leading to a flurry of studies on the newly mapped steroid hormone.

How Aldosterone Works2
Aldosterone is:
- A mineralocorticoid, a class of steroid hormones that regulate water and salt balances
- Produced from cholesterol in the zona glomerulosa of the adrenal cortex
- Part of the RAAS for regulating blood pressure
The main function of aldosterone is to regulate sodium and water reabsorption in the kidneys’ late distal tubule and collecting duct. Increase in aldosterone leads to increase in reabsorption of sodium and water, but also an increase in excretion of potassium. Aldosterone’s role in fluid retention makes it an important player in blood pressure regulation.
The RAAS3
The renin-angiotensin-aldosterone system (RAAS) is an endocrine process that regulates blood pressure by adjusting fluid volume, sodium and water reabsorption, and potassium secretion.
Steps of RAAS
- Trigger: Low blood pressure or low sodium load in the distal tubule
- The juxtaglomerular (JG) cells cleave the enzyme renin from prorenin (kidneys)
- The protein angiotensinogen is created and released from the liver (liver)
- Renin is released into the bloodstream, targets angiotensinogen and cleaves it into angiotensin I (plasma)
- Angiotensin I is converted to angiotensin II by angiotensin-converting enzyme (ACE*) (lungs, endothelial tissue)
- Angiotensin II acts on the zona glomerulosa of the adrenal cortex, stimulating aldosterone release (kidneys)
- Aldosterone stimulates retention of sodium and water – and excretion of potassium – by the kidneys
*”ACE inhibitor” drugs treat hypertension by blocking the creation of angiotensin II, which narrows blood vessels along with stimulating production of aldosterone

As a steroid hormone, aldosterone passes through the cell membrane and binds to receptors that move to the nucleus, leading to mRNA transcription that creates new proteins. This mechanism is slower than the actions of angiotensin, and the effects of increased aldosterone might not be seen until hours or even days later.
What Can Go Wrong
Hyperaldosteronism5
Two years after the structure of aldosterone was finally identified, J.W. Conn described a condition caused by an adrenal gland tumor. The condition, called hyperaldosteronism, resulted in hypertension (high blood pressure) and hypokalemia (low potassium). Now commonly referred to as Conn’s Syndrome, hyperaldosteronism is usually caused by hyperplasia, adenoma (non-cancerous tumor), or carcinoma of the adrenal gland. It may also run in families.
Conn’s Syndrome can also lead to tissue inflammation and fibrosis in the heart, kidneys, and vasculature, sometimes causing chronic kidney issues, congestive heart failure, or ischemic heart disease. Treatment options include the diuretic spironolactone or adrenalectomy surgery.
Addison’s Disease6

Addison’s is a disease of adrenal insufficiency, labeled as Addison’s if caused by an autoimmune destruction of the adrenal glands. The condition results in too little cortisol, aldosterone, and androgens being produced. Symptoms may gradually worsen over time, delaying a diagnosis. Sometimes, however, there is an acute presentation of adrenal crisis with hyperkalemia (high potassium), hypotension (low blood pressure), and hyponatremia (low sodium).
Acute treatment involves administration of hydrocortisone to correct the hormonal deficiency. Afterwards, long-term hormone replacement is needed, with careful monitoring to ensure balance. Liberal salt consumption is encouraged for patients craving it.
How Aldosterone Changes in Space
Apollo Studies7
In early missions, it became apparent that space travel had physiological consequences for crew members. Factors influencing changes in fluid and electrolytes, including aldosterone, have been studied since the 1960s.
In most Apollo missions, 24-hour urine samples were collected before, during, and after space flight from each of the crew members. Blood samples were also taken. Angiotensin I was measured in blood samples, while aldosterone was measured in urine. Samples were pooled together and averaged. Between the preflight and postflight measurements, there was a 488 percent increase in angiotensin I on the first day of postflight recovery and a 57 percent increase in aldosterone in the first day following recovery.

Most astronauts experience weight loss during a mission. Some of this is due to tissue loss from lower caloric intake, which can take days to weeks to gain back. However, weight is usually partially restored within 24 hours, which implies that some weight loss on missions is due to fluid changes. Weight loss often leads to an increase in fluid to compensate for lost tissue. This explains the increase in aldosterone secretion, and consequently the increase in fluid volume, in the first 1-2 days of postflight recovery. Aldosterone secretion is triggered by a drop in fluid volume.
Skylab, Salyut, and Mir: Longer Missions8
Like the Apollo studies, Skylab, Salyut, and Mir aldosterone studies were conducted on urine and revealed consistent increases in plasma aldosterone levels. Experimentation on these flights was especially useful due to the extended length of missions compared to Apollo.
For the crew of Skylab, urinary aldosterone remained elevated for the first month aboard the station, and then returned to normal for the next two months. The 25-day Mir-Aragatz and Salyut-7 flights showed similar results. In most postflight urinary analysis, aldosterone levels were consistently increased. This might be explained by the need to retain sodium and therefore fluid in response to weight loss during a mission.

Countermeasures
Since crew members generally returned to baseline after some time, most researchers have concluded that aldosterone changes will not be of great concern on longer missions. However, since Skylab astronauts had consistently higher levels for a full month, it’s worth considering possible effects of long-term elevated aldosterone.
Patients with hyperaldosteronism, or Conn’s Syndrome, are at risk of hypertension and hypokalemia. In undertaking longer missions, it would be prudent to be prepared with hypertension-mitigating treatments. Potassium supplements should also be considered to counteract potential excessive K+ secretion, especially since so many of the best dietary potassium sources (such as bananas, potatoes, squash, beans, and greens) are perishable and may not be available on longer missions.
Aldosterone is one player in an intricate feedback system regulating bodily fluids and electrolytes. Considering the naturally occurring fluid shifts in space and altered diets on spacecraft, these systems should be further studied to determine how to best maintain homeostasis on long-term missions.
Sources
1. Jonathan S. Williams, Gordon H. Williams, 50th Anniversary of Aldosterone, The Journal of Clinical Endocrinology & Metabolism, Volume 88, Issue 6, 1 June 2003, Pages 2364–2372, https://doi.org/10.1210/jc.2003-030490 / 2. Scott JH, Menouar MA, Dunn RJ. Physiology, Aldosterone. [Updated 2022 May 4]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK470339/ 3. Fountain JH, Lappin SL. Physiology, Renin Angiotensin System. [Updated 2022 Jun 18]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK470410/ 4. Vargas-Rodriguez, Jose & Garza-Veloz, Idalia & Flores-Morales, Virginia & Badillo-Almaraz, Jose & Rocha, María & Valdés-Aguayo, José & Martinez-Fierro, Margarita L. (2022). Hyperglycemia and Angiotensin-Converting Enzyme 2 in Pulmonary Function in the Context of SARS-CoV-2 Infection. Frontiers in Medicine. 8. 10.3389/fmed.2021.758414. / 5. Parmar MS, Singh S. Conn Syndrome. [Updated 2021 Sep 18]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK459197/ 6. Munir S, Quintanilla Rodriguez BS, Waseem M. Addison Disease. [Updated 2022 May 15]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK441994/ 7. Johnston R et. al. Biomedical Results of Apollo. Washington, D.C., NASA, 1975. / 8. National Research Council 1998. A Strategy for Research in Space Biology and Medicine in the New Century. Washington, D.C.: The National Academies Press. https://doi.org/10.17226/6282.
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