Gettysburg Medical News
The Clinical View
by P.E. Hoffsten, MD
6 June 2007

WHAT IS THE RAS SYSTEM?

            In 1899, scientist knew that the kidney secreted a substance that raised blood pressures.   Animal experiments had been done cross circulating blood showing the kidney secreted a substance subsequently called “renin”.  Renin is the word standing for the “R” in the RAS system.  In the 1950’s, it was discovered that renin acted on a protein in the blood called angiotensinogen to produce another hormone called angiotensinogen -1.  Thus came the “A” of the RAS system, the “A” standing for angiotensin.  The prefix “angio” stands for blood vessels.  “-tensin” stood for something that made blood vessels have a higher pressure.  There are other hormones in the system but the name “RAS system” comes from the two hormones renin and angiotensin.  Over the years, the renin-angiotensin system was subsequently found to involve a third hormone called “aldosterone”.  Aldosterone is a steroid hormone that is a potent salt retainer, fluid retainer and the major hormone that rids our body of excess potassium.   

            A patient recently asked what the renin-angiotensin system is and what does it do?  I explained to him as above that there were a number of hormones in this system and that each one played a major part in maintaining blood pressure.  This is a critical hormone system that protects human beings in their “fight-flight” mode.  It raises blood pressure, it causes salt and water retention and it makes hearts thicker and stronger although that is not necessarily a good thing.

            Ten thousand years ago, our ancestors did not always have access to water like we do and many civilizations did not have easy access to salt.  A hormone system to help the body conserve salt and water evolved and was critical in the survival of our major civilizations in the past.  Fortunately, or perhaps unfortunately, we have ready and easy access to water and salt today.  We don’t drink because we are thirsty, we drink for social reasons to have a cup of coffee, a glass of beer, or a glass of pop and salt shakers are freely available on the table and liberally added to our prepared foods that come in cans and packages.  Thus to conserve salt and water in our society today is not an essential need of our bodies but that RAS system is still in us.  Unfortunately, with our pizza, pop, and drive-in fast food it works much too well.  In today’s world, the renin-angiotensin system is a major cause of hypertension that occurs in one-third of our population.  Hypertension is a major contributor to heart attacks and strokes which are major killers, accounting for 600,000 deaths per year in the United States.  The renin-angiotensin system also causes hearts to get thicker which is not necessarily a good thing.  Hearts that get too thick do not fill easily and eventually fail contributing to the five million cases of heart failure in our society each year. 

            The gentleman mentioned above said he had heard that there were a number of drugs that blocked the renin-angiotensin system.  He was interested in what they were, how they worked, and whether he needed such a drug.  One of the first drugs to block this system was called spirolactone (Aldactone) released on the market in the late 1950’s.  This was a drug that blocked the receptor for the hormone aldosterone.  Spirolactone could help person conserve potassium and lose unneeded sodium.  It also was a “nickel’s worth” of an anti-hypertensive drug although not very effective for that purpose.  More recently it has been found to be highly effective medication to prevent congestive heart failure.

            The second drug class acting on the RAS system was found by accident and released on the market in 1981.  Scientists studying the components of snake venom discovered a product called an angiotensin converting enzyme inhibitor (abbr: ACE-I) that made blood pressures drop very low.  This ACE-I was very good for the snake allowing it to catch snake-bitten animals because their blood pressure dropped so low the animal could not run.  Scientists reasoned that a small amount of this component of snake venom might be useful to treat hypertension.  There are about 10 ACE-I’s on the market today  and most of them are now generic and relatively cheap.  Insurance companies and managed drug plans favor these drugs to block the RAS system.  These are very good drugs to prevent congestive heart failure.  They also have a life saving effect after a person has had a heart attack.  They prevent the second heart attack and prevent heart failure after the first heart attack.  Unfortunately, they do not prevent progressive kidney disease in patients with diabetes. 

            The third family of medications blocking the RAS system is called the angiotensin receptor blockers (abbr: ARB’s).  These drugs block the receptor for the most potent hormone of the RAS system.  This hormone is angiotensin-2 and in today’s world in the United States is a highly toxic hormone. Blocking the effect of this hormone has a major impact in preventing heart failure, kidney failure, and hypertension.  Unfortunately, all of the seven drugs on the market in this class are still under patent protection and relatively more expensive.  However, this is the only class of drugs in the RAS system that has been demonstrated to protect against chronic progressive kidney failure in type II diabetes. 

            The newest drug in the RAS system is called a direct renin inhibitor.  This is a drug called aliskiren (Tekturna).  It also is under patent protection at about the same price as the ARB class.  This is an excellent antihypertensive drug with no more side effects than a sugar pill.  Its effect to protect end organ disease such as kidney disease or heart failure has not been demonstrated in humans but studies are in process to see if this drug will be as effective as hoped.  This drug has been shown to be very effective in animals.

            The use of any of the four drug classes mentioned above with or without other medications is often necessary in patients that have high blood pressure.  On average, a person in the United States with high blood pressure will require three different medications in order to adequately control the blood pressure at 120/80 mm Hg.  The previous standards of 140/90 are no longer valid.  There is still major disease that occurs in patients with blood pressures at 140/90.  However, the disease causing process of high blood pressure does seem to be completely stopped when a person has a blood pressure of 120/80 or less.  The benefits of achieving this with medication have been well demonstrated in many large trials. 

            As a group it seems that patients hate to make medications.  But the demonstrated truth is that American lifestyle today is uncontrolled when it comes to salt intake, excessive calorie intake and lack of exercise.  Will anyone of these three steps have a major impact to prevent a disease?  America today does not seem to be interested in “diet and exercise”.  Medications do help and are recommended when a person’s lifestyle cannot be modified to benefit their own health.  The healthcare providers at your local clinics have to deal with blood pressure problems as their most common adult issue.  The healthcare providers at your local clinics can be a major help in arriving at a blood pressure control program that is both economical, effective and side effect free.