Hormonal Regulation

The renin-aldosterone system is an endocrine system which guides the renal absorption of water and electrolytes, thus managing blood pressure and osmoregulation. Activation of the system begins in the kidneys with a small cluster of cells adjacent to the afferent and efferent blood vessels of the renal corpuscle. As the nephrons are filtering blood, juxtaglomerular cells monitor blood pressure. If they detect a decrease in pressure, they release the hormone renin into the bloodstream.

Circulating renin interacts with angiotensinogen, a precursor protein synthesized by the liver, to create angiotensin I. A final step cleaves angiotensin I into angiotensin II, a process achieved by angiotensin-converting enzyme, or ACE, which is released by the lungs.

Angiotensin II temporarily increases blood pressure by contracting smaller blood vessels. It also induces the release of aldosterone from the adrenal cortex of the kidneys. Aldosterone directly stimulates the reabsorption of sodium and the excretion of potassium by the kidneys to maintain electrolyte balance. Moreover, circulating levels of aldosterone stimulate the release of antidiuretic hormone, or ADH, by the hypothalamus in the brain.

Upon reaching the kidneys, ADH upregulates aquaporin channels in the nephrons which increase the water retention in the blood vessels. The combined effects of ADH and aldosterone result in a systemic increase in blood pressure.

High blood pressure, or hypertension, and heart failure are often treated using ACE inhibitors. These drugs prevent the formation of angiotensin II. This lets the blood vessels relax, decreasing blood pressure which in turn reduces the workload of the heart.

The renin-angiotensin-aldosterone system plays an important role during pregnancy where uteroplacental blood flow and salt balance needs to be maintained. During pregnancy, the hormone estrogen stimulates the synthesis of angiotensinogen in the liver. Renin, angiotensin I and II all show progressive increases over the course of pregnancy. In some women, this elevated activation of the renin-aldosterone system results in hypertension and preeclampsia; if not properly managed, a significant source of maternal mortality.