Insight into how our body functions normally can be gained by studying how it functions abnormally. For hypertension, insight can be gained by studying what goes wrong when a tumor secretes large amounts of a hormone that results in hypertension in those on a Western diet. But the result of high levels of this hormone in a group of people on a very different diet is no hypertension. The Yanomami have no hypertension, but have high levels of aldosterone in their blood, as discussed here. In Westerners, high levels of aldosterone are associated with hypertension. What can be the difference? An aldosterone secreting tumor can provide some clues.
Secondary Hypertension
The vast majority of hypertension comes from primary hypertension. However, about 5 to 10% of hypertension comes from secondary causes. The most common secondary cause is primary aldosteronism. About one half of the cases of primary aldosteronism are due to aldosterone producing adenomas, a tumor of the adrenal glands. One half of these aldosterone producing adenomas have a mutation in Kir3.4. This is an inward rectifying potassium channel similar to the channel that we discussed last week. Just like the channel we discussed last week, it brings potassium into the cell to help normalize its resting potential.
In the adrenal gland the zona glomerulosa cells depolarize when stimulated by a high potassium level in the blood stream, or when stimulated by angiotensin II. Through a series of molecular reactions within the cell, the result is aldosterone production. The aldosterone goes into the blood stream. In those on a Western diet, this extra aldosterone will over time result in hypertension, mainly from sodium retention. Sometimes these zona glomerulosa cells form a tumor (adenoma) that produces extra aldosterone.
Aldosterone Producing Adenomas
The present study (1) was a review of the different genetic mutations that have occurred in adenomas that produce aldosterone. When mutations occur in the selectivity filter of the potassium channel Kir3.4, the channel lets in some sodium to replace some of the potassium it lets in. This leads to depolarization of the cell membrane and more aldosterone secretion from the tumor cells. This then results in hypertension in those on a Western diet.
This review article also discussed other channels in the cell that can lead to aldosterone producing adenomas. Other mutations that have been found have occurred in the calcium channels, the calcium ATPase pump, and the sodium potassium ATPase pump. The channel and pumps are involved with the series of molecular reactions mentioned above. The mutations in them also lead to more aldosterone and hypertension.
Cell Membrane Depolarization
When the cell membrane depolarizes, there is a release of calcium from its storage in the endoplasmic reticulum into the cytoplasm of the cell. This release of calcium is also done through calcium channels behaving similarly to the Kir3.4 potassium channels. But instead of bringing potassium into the cell, the channels bring calcium from endoplasmic reticulum into the cytoplasm. Thus a mutation in the calcium channel that would lead to increased release of calcium into the cytoplasm of the cell would have an effect similar to the effect of the mutation in Kir3.4, which also leads to an increase in calcium in the cytoplasm.
The mutations that occur in the sodium potassium ATPase pump would lead to decreased function of the pump. This is the pump that pushes sodium out of the cell and potassium into the cell. When the pump is not functioning well, potassium does not come into the cell as much is needed, and too much sodium remains inside the cell. The result is the same as with the malfunction of Kir3.4. The series of molecular reactions resulting from depolarization occurs, leading to more aldosterone secretion. And with Westerners, this results in hypertension.
High Aldosterone Without Hypertension
We have discussed in the past how the Yanomami have very high aldosterone levels, but do not have hypertension. This is because the diet has a very high potassium sodium ratio. When there is enough potassium in the diet, the kidneys adjust to a high aldosterone level by excreting potassium and water, eliminating hypertension.
However on a Western diet the kidneys cannot adjust to a high aldosterone level. The Western diet does not have enough potassium and has too much sodium. The inadequate amount of potassium in the diet means there is not enough potassium to excrete. And there is no mechanism to excrete excessive sodium, so sodium and water are retained in the body and hypertension results.
So to eliminate the increased risk of hypertension from the Western diet, switch to a high potassium foods diet. Get 3 times as much potassium as sodium (5 times as much is even better) in your diet every day. There are multiple tables on this website to guide you. The tab at the top of the page has links to the tables.
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1. Minireview: potassium channels and aldosterone dysregulation: is primary aldosteronism a potassium channelopathy? Gomez-Sanchez CE, Oki K. Endocrinology. 2014 Jan;155(1):47-55. doi: 10.1210/en.2013-1733. Epub 2013 Dec 20. – abstract only
