Doctors in practice are focused on treating hypertension. A growing number are interested in the cause of primary hypertension so they can prevent it. For several decades, studies on the cause of hypertension have focused on sodium. Only recently has the balance of potassium and sodium as a cause of hypertension been understood. Even so, the balance of potassium and sodium as a cause of hypertension has made its way into recent medical physiology textbooks. But it has not made its way into medical practice. The importance of this balance is not widely realized. And it is not discussed in many of the publications and studies in the medical literature. The majority of studies still focus on sodium. One such study is a recent study (1) that discusses the link of the kidney to blood pressure, and focuses on the kidney's regulation of sodium. It mostly ignores potassium.
The relationship of the kidney to blood pressure has been known for many years. The first connection of the kidney to hypertension was the proposal of Richard Bright almost 200 years ago that abnormal urine production led to increased resistance in blood vessels, raising the blood pressure. Dr. Dahl in the 1960s bred hypertensive rats and showed how a high sodium diet made them hypertensive.
In the 1970s Dr. Guyton and associates showed the physiological link of the kidney with sodium. They showed that the kidney regulates the body's fluid by responding to the pressure of the fluid that flows through kidney blood vessels. The kidney did this by matching urinary excretion of salt (sodium) and water with the dietary intake of salt and water. When you consume sodium it goes into the blood and carries water with it. This expands the amount of blood in the vessels and increases the pressure. A kidney responds to this increased pressure by excreting fluid. And one of the kidney's mechanism to excrete fluid is the excretion of sodium, which carries fluid with it.
Kidney transplantations in rats, and then in humans, also supported the role of the kidney in hypertension. These transplantations showed changes in blood pressure according to the type of kidney transplanted. Dr. Dahl transplanted a kidney from a hypertensive rat into a rat with normal blood pressure and caused hypertension in the rat. He also transplanted a kidney from a normal blood pressure rat into a salt sensitive hypertensive rat and showed that the hypertension was reduced. Others have shown similar results by repeating these experiments in other types of hypertensive and non-hypertensive rats.
Kidney transplantation in humans has had similar results. A patient with resistant hypertension requiring a kidney transplant will have relief of the hypertension if the kidney transplant is from a patient without hypertension.
In the 1980s, Dr. Hall and associates showed that angiotensin II acted on the kidney to change blood pressure. Later it was shown that angiotensin II acts on the sodium channels in cells in the kidney tubule. Similarly, the effect of aldosterone on blood pressure was shown through various experimental procedures.
More Recent Work
Most recently it has been shown how aldosterone works at the molecular level within the kidney tubule cells. This important work shows how sodium and potassium interact with each other and with bicarbonate in the kidney to affect blood pressure. See our post here about how this is done. This specific work is not mentioned, but the author does discuss some similar work showing that aldosterone promotes potassium excretion. This is the only discussion of potassium in the article.
There are also other cellular interactions in the kidney that influence blood pressure. Many of these interactions function by acting on the regulation of sodium and potassium. WNK genes are an example. WNK stands for With No K (K is not potassium, but is a short-hand symbol for lysine). WNK genes are part of a network of kinases. The network regulates sodium and potassium in kidney cells. WNK does this by regulating the sodium transporters that reabsorb sodium in the distal nephron of the kidney. By doing this it affects the balance of sodium and potassium inside and outside the cell, and thus affects the cell membrane potential. Affecting this balance affects blood pressure and can eventually result in hypertension.
Other publications adding to the basic model of fluid retention and sodium potassium balance have been studies looking at the collection of fluid (extracellular fluid) between blood vessels and cells of the body outside the kidney. One area that has been investigated is in the skin, where sodium is collected in a greater concentration that it is in the blood. Sodium collects here because of certain types of proteins found in the skin. These unique proteins allow a collection of sodium accompanied by less water than in other parts of the body. This skin collection may be involved with some of the unexpected fluctuations in total body sodium in blood pressure that occur over the long term. These fluctuations were previously unknown but were discovered during studies to prepare for the Mars expedition.
Mars Helps Out
Physiological work being done on subjects in preparation for a trip to Mars is giving some excellent data and expanding our knowledge of how sodium balance occurs. Among the data being collected is the relationship of sodium intake and sodium excretion. These are long-term studies because of the expected length of the trip to Mars. One study was for 105 days and another for 205 days.
Among the many findings, the researchers have found that sodium will fluctuate from day-to-day even when the sodium intake is the same every day. This fluctuation follows an infradian pattern. An infradian rhythm is a rhythm that lasts longer than a circadian rhythm. Prior assumptions had been made that sodium and potassium balance occurred in a day. This was the reasoning behind spot and 24 hour urine collections. A 24 hour collection would capture the amount of sodium consumed during those 24 hours.
There are a number of speculations on how this infradian pattern occurs, and these speculations are presently being investigated. This infradian pattern has led to interesting findings concerning the accuracy of urinary fluid collection. As discussed in a previous post, a collection of urinary sodium reflects the amount of sodium ingested the previous day only 50% of the time. For 75% accuracy, 3 days should be averaged. And for a 92% accuracy, 7 days would need to be averaged.
The article also discusses the potential of immune mechanisms being involved with hypertension. It discusses that there may be immune reactions that have separate, independent effects on blood pressure.
However in this case, it is difficult to distinguish cause from effect. Rather than immune reactions causing increased blood pressure, the immune reactions and increased blood pressure may both result from the cellular response to sodium potassium imbalance. As was discussed in the post on heart failure, cellular death from a poor potassium sodium ratio will lead to scar tissue because of an inflammatory response. In that case, the immune reaction was caused by the cell death that occurred from potassium sodium imbalance.
Small studies have been done that show immunosuppression will lower blood pressure in hypertensives who have rheumatoid disease. The article discusses the various cytokines (molecules involved in the immune response) and the various inflammatory cells that may affect blood pressure. These cells and molecules almost certainly are involved in end-organ damage. If the organ that is damaged by the inflammation is the heart, kidney or blood vessels, then blood pressure should be improved by suppressing the inflammation.
Studies show that damage in the kidney blood vessels looks like the damage in the heart discussed above. At the tissue level the vessels show an inflammatory response when examined under the microscope. This inflammatory response looks very much like the response that researchers have described in animal hearts with experimental hypertensive heart failure.
The present article has only a limited discussion of the role of potassium and the kidney in hypertension. And it does not try to integrate its discussion of sodium with a discussion of the known mechanisms of potassium on blood pressure. But the author does give an excellent overview of sodium's effect on blood pressure. As the basic understanding at the cellular level of how sodium and how potassium perform within the cell becomes better known, it will be more and more difficult for clinical articles to claim harm to healthy individuals from a sodium intake of 1500 mg or 2300 mg.
1. The inextricable role of the kidney in hypertension. Crowley SD, Coffman TM. J Clin Invest. 2014 Jun;124(6):2341-7. doi: 10.1172/JCI72274. Epub 2014 Jun 2.