Renin-angiotensin system (RAS)
The renin-angiotensin system (RAS) is a crucial hormone system in the human body responsible for regulating long-term blood pressure. It operates through a sequence of enzymes and hormones produced by organs such as the kidneys, liver, and lungs. When blood pressure drops, the RAS activates to initiate a physiological response aimed at increasing pressure. Central to this system is the enzyme renin, which converts a dormant hormone, angiotensin, into angiotensin I. Angiotensin I is then transformed into the more potent angiotensin II by the angiotensin-converting enzyme (ACE) found in the lungs. Angiotensin II plays a significant role in raising blood pressure by constricting blood vessels and stimulating aldosterone release, which helps regulate sodium and water filtration in the kidneys.
Medical research on the RAS has led to the development of effective treatments for conditions like high blood pressure and heart disease, including ACE inhibitors and angiotensin receptor blockers (ARBs). These medications help modulate the effects of the RAS, offering therapeutic benefits, particularly for patients at risk for diabetes and kidney disease. Ongoing studies continue to explore the complexities of the RAS, including variations in how different populations respond to treatments, providing insights into personalized medical care.
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Renin-angiotensin system (RAS)
The renin-angiotensin system (RAS) is a hormone system in the human body that regulates long-term blood pressure. The system works by producing a series of enzymes and hormones that act together to maintain a healthy blood pressure. These substances are produced by various organs, including the kidneys, liver, and lungs. If blood pressure drops too low, the RAS initiates a physiological chain reaction to increase the pressure. Medical study of the RAS has also allowed doctors to gain insight into the treatment of high blood pressure. Researchers have developed several medications that can modify or block the hormone-producing capabilities of the RAS and help patients lower their blood pressure.
Background
Blood pressure is the force of blood pushing against the walls of the arteries. High blood pressure occurs when this force pushes too hard on the arteries and causes the heart to overexert itself to maintain proper blood flow. This condition could be caused by a narrowing of the artery wall or the blood encountering resistance as it flows through the body. Over time, high blood pressure can damage arteries and lead to heart attack, heart failure, stroke, diabetes, or kidney disease.
In the late nineteenth century, Finnish medical scientist Robert Tigerstedt and medical student Per Bergman theorized that an enzyme produced by the kidneys was responsible for increasing blood pressure in rabbits. They called this hypothetical substance renin. In 1934, pathologist Harry Goldblatt discovered that restricting the flow of blood to the kidneys led to an increase in blood pressure. Since blood carries oxygen throughout the body, Goldblatt suggested that a reduction in oxygen to the kidneys must have triggered the production of a substance that raised blood pressure. Researchers attempted to isolate the substance in the hopes that it could be used in the production of medication. What they found, however, was that it was not the renin itself that produced the change in blood pressure. The renin was just a catalyst that converted hormones in the bloodstream into a pressure-raising substance called angiotensin. It was later discovered that there were two forms of this hormone, angiotensin I and angiotensin II.
Overview
The renin-angiotensin system responds to changes in blood flow to the kidneys. The kidneys are two fist-sized organs located in the back of the abdomen. They are responsible for filtering out impurities from the blood and regulating several bodily systems. If the kidneys experience a drop in blood flow—such as from significant blood loss or dehydration—specialized cells within the organs will increase the production of renin. Renin is an enzyme, a protein that acts as a catalyst and produces a biochemical reaction in other substances. Once released into the bloodstream, the renin drifts until it encounters dormant hormones known as angiotensin. Angiotensin is produced in the liver, an organ that filters the blood and removes toxins.
The renin reacts with the angiotensin and converts it into angiotensin I. This hormone is able to raise blood pressure to a degree, but cannot effect large-scale changes. Instead, it must first be converted into a more powerful hormone called angiotensin II. This is done with the help of a catalyzing molecule called angiotensin-converting enzyme (ACE), which is produced in the lungs. One of the main functions of angiotensin II is to constrict the walls of the arteries and raise blood pressure. It also stimulates the release of the hormone aldosterone from the adrenal glands—hormone-producing glands located near the kidneys. While aldosterone has significant artery-constricting proprieties, it is also able to send a chemical signal to the kidney to regulate the filtration of sodium and water in the bloodstream. An increased amount of water in the bloodstream will lead to an increase in blood pressure.
When blood pressure returns to normal, the kidneys scale back their production of renin. Angiotensin I, angiotensin II, and aldosterone will eventually be broken down by the body. The renin-angiotensin system constantly produces a baseline amount of renin to maintain a healthy regulation of blood pressure. Under normal circumstances, increased activity in the RAS occurs only in response to a drop in blood flow.
Understanding how the system works has allowed doctors to make significant advancements in the treatment of high blood pressure, heart failure, and kidney disease. Researchers have developed medications known as ACE inhibitors that block the angiotensin-converting enzyme from turning angiotensin I into angiotensin II. Regulating the amount of ACE inhibitors allows doctors to prompt the body to constrict or widen its arteries in accordance with a diagnosis. The medications are also often used to treat diabetes—a condition where the bloodstream contains too much glucose, or sugar—because diabetics are more prone to suffer from high blood pressure or kidney disease. Other medications known as angiotensin receptor blockers (ARBs) prevent angiotensin II from reacting with the arterial walls and causing them to constrict.
Despite the advancements made in studying the renin-angiotensin system, doctors are still trying to find answers to several questions, and they are discovering new questions in the process. Some patients suffering from high blood pressure respond differently to treatment than others. For example, African Americans usually do not respond as well to ACE inhibitors as do individuals from other ethnicities. Scientists theorize that this may be because their bodies respond differently to the drugs, making their renin-angiotensin systems less sensitive to blocking agents. Other research into the RAS has hinted that the biological switch needed to activate the hormone angiotensin II may be found in many tissues of the body. Studies have also discovered new enzymes that may be part of the RAS, and researchers are investigating the possibility that renin itself may be able to directly affect angiotensin II production.
Bibliography
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