Renin-angiotensin-aldosterone System – Cardiovascular Pharmacology

by Joseph Alpert, MD

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    00:01 angina and heart failure, they are number one.

    00:01 Okay. Let’s take a look now at another drug category. Let’s look at the renin–angiotensin system. This is part of the system that your body has for regulating blood pressure and blood volume. Remember, in the physiology area, we talked about the meticulous control that the central nervous system maintains over the circulation. For example, if you suddenly walk into the desert, where I live in Arizona on a hot day, you are going to get very, very dehydrated if you are not drinking water. Well, the body has a system - the renin–angiotensin system, for holding on to salt and water. It doesn’t allow the kidneys to make as much urine and eliminate salt and water. You hold on to fluids more because you stimulate the renin–angiotensin system. The body has a whole series of nervous connections and… and little monitors throughout the cardiovascular system that enable it to tell, “Hey, things are dehydrating. Blood volume is going down. Let’s rev up the renin–angiotensin system.” Chemicals are released; Rennin, from the kidney that converts in the bloodstream to a… to an agent called “angiotensin” that clamps down the blood vessels, raises the blood pressure and also has effects on the kidney to prevent salt and water excretion.

    01:24 Now, it turns out, in heart failure, often the body misreads the signal. It sees there’s decreased circulating blood volume and it thinks, “Oh, it’s dehydration,” or, “Oh, it’s blood loss. I’d better hold on to salt and water.” But actually, the problem isn’t dehydration and it isn’t hemorrhage, it’s that the heart is just pumping less. And when that happens, the body misreads it. It holds on to salt and water and that results in excess salt and water in the lungs, leading to shortness of breath.

    01:57 And remember, when we did the physical exam, I showed you the edema on somebody’s leg? That’s also the result of excess renin–angiotensin activity in heart failure. So, in that setting, we would like to block the renin–angiotensin system. We would like to say, “No, no, don’t hold on to salt and water.” We want to have the kidney excrete salt and water because we already have too much on board because of the heart failure state. And so, blockers were developed for the renin–angiotensin system. Just as we had blockers for the beta-stimulated sympathetic nervous system. Now we have blockers for the renin–angiotensin system. There’s two classes of blockers for the renin–angiotensin system - so-called “ACE inhibitors”, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. They block the pathway in different places. I am going to show you the pathway in a moment. I am not showing it to you yet because it’s fairly complex and I don’t expect you to be memorizing it, but I am going to show it to you. It’s one of the critical things that we teach to medical students early in their career and continue to emphasize throughout their clinical training.

    03:09 Now, let’s talk a little bit about using the ACE inhibitors - angiotensin-converting enzyme inhibitors, and the angiotensin receptor blockers for the heart failure state. What do they do? They dilate the blood vessels and particularly, they tell the kidney, “Hey, let’s excrete more salt and water.” They do this through a complex system that involves the adrenal and hormones from the adrenals. I don’t want to go into this in great detail because it would take quite a long time and it’s beyond what you need to know. But, the important thing for you to know is that the angiotensin-blocking enzyme and the receptor blockers work in the kidney and they allow the kidney to excrete salt and water. Now, if you were dehydrated, you wouldn’t want to take one of these because it’s going to make the dehydration situation worse and lower your blood pressure and so forth. But, if you are in a heart failure state, you want to excrete that salt and water. And guess what? You get a second bonus, you lower blood pressure. So, just like the beta blockers, you are decreasing the work of the heart. So, there’s sort of double benefit, if you will, in the heart failure patient. You are actually making the work of the heart less, at the same time that you are encouraging excretion of salt and water, so that the edema - the swelling in the legs, the swelling in the liver, the swelling in the… in the lungs, gets better. Now, this is the entire angiotensin-renin receptor sequence in the body and it’s complicated. But, you can see with the little red arrows, the one that says “ACE-I,” that’s the ACE inhibitor, where it blocks this system.

    04:52 And off to the left, you can see the angiotensin receptor blockers, it blocks the system a little later on. The important thing to remember here is again, we are doing what we did with beta blockers. We are blocking an excessive effect of one of the body’s natural defenses because the body has misinterpreted the situation. It’s thinking there’s dehydration or loss of blood, when in fact, the problem is decreased pumping by the heart. Now, if you would like, you are more than welcome at your leisure to go over this and understand the whole sequence.

    05:26 It starts with release of renin from the kidney that’s converted in the bloodstream to angiotensin.

    05:31 Angiotensin I goes to angiotensin II. That stimulates the adrenals to release a hormone, aldosterone, that holds on to salt and water. You can see all of this works in an attempt to restore blood volume. With the blockers, we don’t want to restore blood volume, it’s already excessive. The body has misread the signal. We want to release salt and water and the ACE inhibitors and the angiotensin receptor blockers help.

    05:57 Now, it turns out there are a number of side effects. If the patient has decreased kidney function, these drugs can actually make the kidney function worse. Another thing that happens is with ACE inhibitors, it is possible that you will lower the blood pressure too much and also, there can be allergic reactions with the ACE inhibitors. There’s much less problem with the angiotensin receptor blockers. They are much better tolerated. And so, in elderly and frail individuals, we often will go with the angiotensin receptor blockers.

    06:27 Here’s a list of all the drugs. You can see all the drugs that end in “pril” are ACE inhibitors and all the drugs that end in “artan”, for example, losartan, are the angiotensin receptor blockers. You are not going to memorize these or the doses.

    06:44 I just put them up to show you there’s a whole variety of these. And guess what the good news is? Almost all of these are generic and so therefore, very reasonably priced and they are among the most commonly prescribed drugs. They are used as first line for hypertension, they are used as first line for heart failure, they are used as first line for ischemic heart disease - for atherosclerotic heart disease. Now, as I said before, the side effect potential is a little more with ACE inhibitors and a little less with angiotensin receptor blockers.

    07:19 But both of them can cause worsening of kidney function when they are given to patients particularly who already have some kidney disease. For example, diabetics who always have a tendency towards kidney disease. Often you can make that worse, so you have to monitor kidney function. Again, you have to have an integrated clinical plan and you have to follow up carefully on the patient. Let’s finally talk about a third class of

    About the Lecture

    The lecture Renin-angiotensin-aldosterone System – Cardiovascular Pharmacology by Joseph Alpert, MD is from the course Introduction to the Cardiac System.

    Author of lecture Renin-angiotensin-aldosterone System – Cardiovascular Pharmacology

     Joseph Alpert, MD

    Joseph Alpert, MD

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