The renin–angiotensin system (RAS) is a hormone system that regulates blood pressure and fluid balance. When blood volume is low, cells in the kidneys secrete a protein, renin, directly into circulation. Renin is a vitamin D regulated gene. Unlike many other genes, renin is down-regulated or decreased by vitamin D.
After being secreted by the kidneys, renin converts a prehormone, angiotensinogen, secreted by the liver to angiotensin I. Angiotensin I is subsequently converted to angiotensin II by the enzyme angiotensin converting enzyme (ACE) found in the lungs. Angiotensin II causes blood vessels to constrict, resulting in increased blood pressure.
Angiotensin II also stimulates the secretion of the hormone aldosterone from the adrenal gland. Aldosterone causes the kidneys to increase the reabsorption of sodium, potassium, and water into the blood. This increases the volume of fluid in the body, which also increases blood pressure. If the renin–angiotensin–aldosterone system is too active, blood pressure will be too high.
There are many drugs that work to interrupt different steps in this system and in consequence, try to lower blood pressure. Inhibitors of angiotensin-converting enzyme (ACE inhibitors) are often used to reduce the formation of the more potent angiotensin II. Commonly prescribed ACE inhibitors include perindopril (trade names are Coversyl or Coversum), captopril (Capoten), enalapril (Vasotec), lisinopril (Prinivil or Tensopril), and ramipril (Altace ).
Since aldosterone is responsible for increasing the excretion of potassium, one downside to using ACE inhibitors can cause retention of potassium, causing high blood potassium or hyperkalemia. Some people, however, can continue to lose potassium while on an ACE inhibitor. Potassium supplementation should be used with caution owing to the hyperkalemic effect of ACE inhibitors.
Recently, Dr Davide Carrara and associates of the University of Pisa in Italy studied the effects of repleting vitamin D in fifteen consecutive ACE inhibitor-free patients, also on a salt-free diet with essential hypertension and vitamin D deficiency.
Carrara D, Bernini M, Bacca A, Rugani I, Duranti E, Virdis A, Ghiadoni L, Taddei S, Bernini G. Cholecalciferol administration blunts the systemic renin-angiotensin system in essential hypertensives with hypovitaminosis D. J Renin Angiotensin Aldosterone Syst. 2013 Jan 2.
The authors began their paper very clearly, “A number of observations suggest a close relationship between vitamin D and cardiovascular disease in humans. Vitamin D plasma levels inversely correlate with blood pressure and cardiovascular disease and mortality, and intervention studies indicate that vitamin D therapy improves cardiovascular risk profile.” They also opined, “The link between this vitamin and cardiovascular disease is solid.”
Then, they reported on their study. The authors gave the 15 patients 25,000 IU/week of vitamin D3 for two months. At the end of the study, they observed a significant reduction in blood renin and aldosterone and an insignificant reduction of angiotensin II.
However, they warned that patients on ACE inhibiters who are not on a salt-free diet may not show the same effect on their RAS. They also warned that they only studied 15 patients, adding “they were well selected and free from drugs interfering with RAS (such as ACE inhibitors).”
“Our data indicate that in essential hypertensive patients with hypovitaminosis D under constant salt intake and free from drugs interfering with RAS, chronic vitamin D receptor stimulation blunts systemic RAS activity.”
This is the first human study to show vitamin D has positive effects on the RAS system and gives a clear mechanism by which vitamin D likely, but perhaps only modestly, reduces blood pressure in humans.