Renin is an enzyme with hormone-like effects. It is produced in the kidney and plays a role in regulating blood pressure.
What is renin?
The name renin is derived from the Latin “ren” for kidney. It is an enzyme that has a hormone-like effect. Renin is produced in the kidney of vertebrates. The release of renin occurs, among other things, when blood pressure is low. Catecholamines can also increase renin release. However, key stimuli for renin secretion are always associated with a drop in blood pressure. Renin is the initiator of the renin-angiotensin-aldosterone system (RAAS). This serves to increase blood pressure. Renin was discovered in 1898 by the Finnish physiologist Robert Adolph Armand Tigerstedt. The enzyme renin consists of two lobes. Between these two lobes is a cleft containing the active site of the enzyme with two catalytic aspartate groups. The inactive precursor of renin is also called prorenin. It is additionally equipped with an N-terminal propeptide. A hundredfold higher concentration of prorenin than of renin is found in blood plasma.
Function, action, and roles
Renin is an important part of the renin-angiotensin-aldosterone system. The RAAS is a regulated circuit formed by various enzymes and hormones that controls water and electrolyte balance in the body. The RAAS is one of the most important blood pressure regulating actions of the body. The renin-angiotensin-aldosterone cascade begins with the release of the enzyme renin. The enzyme is formed in the juxtaglomerular apparatus of the kidney. This consists of specialized connective tissue and blood vessel cells and of the macula densa. Specialized cells of the urinary tubules are found in the macula densa. The juxtaglomerular apparatus has the task to measure the blood pressure in the feeding vessel of the kidney. At the same time, it also measures the salt content in the urinary tubules and responds to signals and stimuli from the autonomic nervous system. Various hormones also influence the activity of the juxtaglomerular apparatus. When the juxtaglomerular apparatus detects decreased blood flow to the renal corpuscles, increased renin is released. Also, when decreased blood pressure is measured at the baroreceptors, the blood pressure sensors of the vas afferens, renin is released. Increased release of renin is also initiated when there is a decrease in the amount of fluid in the renal corpuscles. The decrease in glomerular filtration rate (GFR) also leads to increased secretion, as does a decreased concentration of saline ions in the urine. Salt sensors in the macula densa of the juxtaglomerular apparatus are responsible for the measurement. In summary, renin is released whenever blood pressure drops and/or there is a threat of loss of saline and water. Renin has a protein-splitting effect and cleaves the protein angiotensinogen, which is formed in the liver. This produces angiotensin I. This is converted into angiotensin II by the angiotensin converting enzyme (ACE). Angiotensin II is the end product of the renin-angiotensin-aldosterone cascade. It causes constriction of the small blood vessels. This increases blood pressure. In the adrenal cortex, angiotensin II also leads to a release of aldosterone. Aldosterone is a hormone that promotes the reabsorption of water and sodium in the kidney. This mechanism also increases blood pressure.
Formation, occurrence, properties, and optimal levels
Renin is formed predominantly in the cells of the juxtaglomerular apparatus. The precursors required for this are modified in the endoplasmic reticulum and Golgi apparatus of renin-producing cells after translation. However, renin is synthesized not only in the kidneys but also in several other organs. Extrarenal sites of renin production include the uterus, adrenal glands, pituitary gland, central nervous system, and salivary glands. However, the main production occurs in the kidneys. Renin levels are determined in blood plasma. Normal values are 2.90 – 27.60 pg/ ml in recumbent adults. In standing adults, normal values increase to 4.10 – 44.70 pg/ ml.
Diseases and disorders
An unnaturally high renin level occurs, for example, with low sodium intake, low blood pressure, or fluid deficiency. Laxatives, diuretics, and some hormonal contraceptives also increase blood renin levels.In the case of overproduction of aldosterone (primary hyperaldosteronism), on the other hand, the renin value may be lowered. Unnaturally low values occur in patients with diabetes mellitus or with a very high sodium intake. Renin also plays an important role in the development of high blood pressure (hypertension). In many cases, high blood pressure is caused by a narrowing of the renal artery, a so-called renal artery stenosis. This stenosis is usually caused by arteriosclerosis. Cholesterol degradation products and other substances are deposited in the vessel wall. The wall thickens, making it much more difficult for the blood to flow through the affected vessels. In the course of renal artery stenosis, so-called renal hypertension develops. This is triggered by the Goldblatt mechanism. The Goldblatt mechanism ensures that reduced renal blood flow leads to the release of renin and thus to the activation of the renin-angiotensin-aldosterone system. Due to the increase in renal water and salt retention and vasoconstriction, blood pressure is increased. Thus, arterial hypertension develops. However, renal hypertension usually develops when the renal artery is more than 75 percent obstructed. If the renal artery is narrowed to a lesser degree, the patient may be asymptomatic. A renin-producing tumor can also lead to hypertension via activation of the RAAS. The same is true for renal cell carcinoma, chronic pyelonephritis, cystic kidneys, and glomerulonephritis.
