Primary hypertension can be prevented by a high potassium foods diet. Primary hypertension is the cause of hypertension in 90 to 95% of people. However 5 to 10% of people will have secondary hypertension, in which hypertension is caused by another condition. The most common cause of secondary hypertension is primary aldosteronism. Aldosterone producing adenomas account for approximately 30-50% of primary aldosteronism.
Understanding how these tumors cause increased aldosterone secretion may help with understanding how increased aldosterone secretion occurs in primary hypertension. And it may help with understanding how diet affects aldosterone secretion. So far, all studies of these tumors support the importance of the dietary potassium sodium ratio for determining aldosterone secretion and preventing hypertension.
The present publication (1) comments on an article discussing one of the possible causes of aldosterone producing adenomas. It first reviews how aldosterone is secreted and then reviews some of the mutations that lead to aldosteronism.
Where Aldosterone Is Produced
Aldosterone is produced by cells in the zona glomerulosa of the adrenal gland. These cells maintain a negative membrane resting potential by regulating the permeability of potassium. When they are stimulated with a high level of potassium in the blood, angiotensin II, or ACTH, these cells depolarize. Potassium leaves the cell and sodium enters. This results in an opening of calcium channels with an increase of calcium in the cytoplasm of the cell. The increase of calcium in the cytoplasm activates the calcium calmodulin pathway. This activation leads to an increase in the enzyme that converts a precursor molecule into aldosterone.
How Tumors Increase Aldosterone Production
Tumors that secrete aldosterone originate from cells in the zona glomerulosa of the adrenal gland. Until recently the cellular mechanism that increased aldosterone secretion by these cells was unknown.
Researchers' understanding of aldosterone producing adenomas took a major step forward in 2011. In 2011 it was discovered that 30% of the adenomas had a somatic mutation in the selectivity filter of the potassium channel Kir3.4. This is an inward rectifying potassium channel, which means that the channel moves potassium from outside the cell to inside. This direction is opposite to the direction that the main potassium channels move potassium. The selectivity filter allows potassium to pass through the channel, but keeps out other ions, such as sodium.
Since the 2011 discovery, other mutations have been found in the selectivity filter and in other parts of the Kir3.4 channel. Many of these mutations are familial, resulting in inheritable changes that can be passed on to subsequent generations. These changes lead to excessive aldosterone production and hypertension in recognized familial disorders.
What The Mutations Do
There have been mutations also found in other channels and pumps besides Kir3.4. All of these have in common the reduction of membrane potential (depolarization), increased sodium inside the cell, opening of calcium channels, and increased production of enzymes involved in making aldosterone. These other mutations include mutations in sodium potassium ATPase, membrane calcium ATPase, and at least one of the calcium channels.
A reduction in the sodium potassium ATPase activity reduces the membrane potential and leads to increased aldosterone production. Angiotensin II lowers sodium potassium ATPase activity to stimulate aldosterone secretion. With a reduced cellular membrane potential, angiotensin II will more quickly and more often stimulate aldosterone secretion.
Malfunction of other potassium channels can lead to abnormal aldosterone secretion. The most prevalent potassium channels in the zona glomerulosa cells are TASK-1 and TASK-3. In mice, the deletion of the genes for TASK-1 and TASK-3 causes abnormal aldosterone production responsive to diet. But in human aldosterone producing adenomas, no abnormalities of these channels have been found yet.
However a recent article (2) found that TASK-2 (previously not known to be present in zona glomerulosa) was present in zona glomerulosa cells and was decreased in aldosterone producing adenomas. This paper was the first to show that TASK-2 was present in zona glomerulosa cells. Its activity normally is on the order of 1% to 10% of the activity of TASK-1. So this low level of activity makes it unclear whether a reduction in its activity would lead to aldosteronism.
Cell Membrane Potential Is Key
But in all cases, the stimulation for more aldosterone secretion is a reduction in the cell membrane potential (depolarization), an increase in the concentration of sodium inside the cell, and an increase of calcium inside the cell. These tumors show what conditions in aldosterone producing cells lead to increased aldosterone production.
So once again we have an article in the medical literature showing the importance of the membrane potential of the cells in the adrenal gland that secrete aldosterone. The depolarization of this membrane is what leads to secretion of aldosterone. The membrane potential is determined by the balance of potassium and sodium inside and outside the cell. Any factor that impedes potassium re-entry into the cell or enhances sodium entry into the cell will lead to a lower membrane potential and increased depolarization. And in the zona glomerulosa of the adrenal gland, the change in membrane potential will lead to increased aldosterone secretion.
How The Western Diet Is Like A Tumor
The Western diet leads to the same type of membrane depolarization as found in the aldosterone producing adenomas. With inadequate amounts of potassium and excessive sodium in the diet, the zona glomerulosa cells will be unable to get enough potassium inside the cell and will have too much sodium inside the cell. This will lead to increased aldosterone secretion, as occurs in the hypertension of those who are on a typical Western diet loaded with sodium and deficient in potassium.
The increased aldosterone will lead the kidney to produce more channels to eliminate potassium and recycle sodium. But the low level of potassium means the kidney has little potassium to excrete. The excessive sodium has no mechanism to be excreted in larger amounts, so it will be retained along with the water that accompanies it. The continued extra fluid that accompanies sodium eventually leads to hypertension, as described in the hypertension model developed by Dr. Guyton several decades ago.
These mutations in potassium channels have confirmed the mechanism that leads to hypertension. The adrenal zona glomerulosa cells are chronically depolarized at a lower level of potassium than normal. This leads to an increased aldosterone secretion, resulting in the hypertension that accompanies these tumors.
This same mechanism is invoked by the Western diet. To avoid the hypertension that eventually results from such a diet, start a high potassium foods diet. By getting enough potassium and less sodium you will be keeping the cell membrane at an appropriate level and will be allowing your kidneys to get rid of excess fluid. You will be rejecting the inevitable hypertension that later occurs in 90% of Westerners who have normal blood pressure at age 55.
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1. Channels and pumps in aldosterone-producing adenomas. Gomez-Sanchez CE. J Clin Endocrinol Metab. 2014 Apr;99(4):1152-6. doi: 10.1210/jc.2014-1062.
2. Lower expression of the TWIK-related acid-sensitive K+ channel 2 (TASK-2) gene is a hallmark of aldosterone-producing adenoma causing human primary aldosteronism. Lenzini L, Caroccia B, Campos AG, Fassina A, Belloni AS, Seccia TM, Kuppusamy M, Ferraro S, Skander G, Bader M, Rainey WE, Rossi GP. J Clin Endocrinol Metab. 2014 Apr;99(4):E674-82. doi: 10.1210/jc.2013-2900. Epub 2013 Nov 27.
