How Blood Pressure Works, Part 1

On one level, blood pressure is pretty simple:

Squeeze in more blood volume into the body, and blood pressure goes up.

If the heart works harder, blood pressure goes up.

If it's harder to get the blood through all those pipes, blood pressure goes up.

All blood pressure medications work on one (or more) of these three principles.

But when we look deeper, to see what these medications are actually doing and how they work, we find that evolution has worked out an very complex system to regulate our blood pressure within a narrow range.

Why so complex? To keep the blood flowing to our brains, and everything else, as we go from laying, to sitting, to standing, to running and and jumping. And all the while, keeping the pressure low enough to not break anything -- all those delicate fine blood vessels in the kidneys, eyes, brain, and elsewhere.

And that's why it's important to intervene when things go wrong, and our blood pressure gets too high or too low.

Our story covers everything from the kidneys and adrenal glands to the bloodstream to the lungs, the brain, the heart -- even the little blood vessels in our feet play a role.

So let's look at blood volume, first. Blood is mostly water, and regulating blood volume means adjusting how much water we hold in our bloodstreams. This is done through a complex network of mechanisms.

We'll start with one that's a bit indirect -- the renin-angiotensin-aldosterone loop. It's indirect, but as we'll see, it's in the middle of everything, so it's hard to talk about the rest without covering this one first.

The body's main sensor for blood pressure is the kidney. When the blood pressure or the difference in pressure between the inlet and outlet of the kidney is too low, the kidney increases its output of renin (pronounced "reenin").

Renin in the bloodstream splits a protein in the blood called angiotensingen. One piece of this is called angiotensin I.

Angiotensin I doesn't do much, but in the lungs, it encounters Angiotensin Converting Enzyme (ACE). And already, we find a drug target. So-called ACE inhibitors block the action of this enzyme, so it cannot convert angiotensin I to angiotensin II.

But there's another pathway that can convert angiotensin I to angiotensin II, so sometimes these drugs stop working. We have an alternative to solve that problem, that we will get to in a minute. And ACE inhibitors in a minority of people, can cause a dry cough. Blocking angiotensin conversion leads to production of bradykinin and substance P in the lungs, which irritate the vagus nerve, leading to the cough. So if you're in that minority, or have asthma, you may need that alternative, too.

Angiotensin II is the nasty stuff. It causes thirst, higher cardiac output, cardiac hypertrophy (the heart gets bigger), increased vascular resistance (the pipes resist the flow of blood).

All of these things cause the blood pressure to rise.

But there are two things it does in particular that are noteworthy. One, it tells the pituitary (at the base of the brain) to release a hormone known as either AVP (arginine vasopressin) or ADH (anti-diuretic hormone). This tells the kidneys to hold onto water.

The other is that it tells the adrenal glands to make aldosterone. Aldosterone is a steroid hormone that regulates the balance between potassium and sodium in the blood. Water follows the sodium, through osmosis. If the kidneys let sodium escape, a good deal of water will follow it, and blood pressure will drop.

Aldosterone tells the kidneys to readsorb sodium, in exchange for potassium. That helps keep the blood volume up. Without enough blood volume, we may not have enough to reach the brain when we stand up, and can feel dizzy or even pass out on standing. But retaining too much sodium raises our blood pressure.

Angiotensin Receptor Blockers (ARBs) help put a stop to all that nonsense. They block the action of angiotensin II.

The actions of aldsterone can be blocked with a drug called spironolactone, which blocks the adlosterone receptors

For some of us, sodium (as in salt) gets retained, often because of an excess of aldosterone, often due to too much angiotensin II. (There's another hormone, ANP, produced by the heart, that tells the kidneys to get rid of sodium.) For these people, with salt-sensitive hypertension, reducing the sodium in their diet will lower blood pressure. (The rest of us just get rid of any excess in our urine).

Regulation of blood volume all comes back to the kidneys. The pressure is sensed by the kidneys, and the kidneys are responsible for both the water balance and managing potassium and sodium (and a good deal more).

Some have more problem with too much blood volume, so diuretics are used. These come in two main flavors -- ones that get rid of potassium, and ones that don't ("potassium sparing"). Restricting sodium also helps these people. There are even drugs which oppose the action of aldosterone -- helping let sodium escape. (Some people make too much aldosterone even without the angiotensin II signal).

It's important to choose one that maintains potassium levels within range, because potassium being too low or high can cause heart arrythmias, or even a heart attack.

ACE inhibitors have been shown to help protect the kidneys from diabetes damage. It's likely that ARBs do this as well, but this isn't as well-studied as the benefits from ACE inhibitors, so those are often what's recommended to diabetics.

And one of the causes of high blood pressure is kidney damage. The goal is to stop high blood pressure before it becomes a downward spiral toward a bad end.

We've covered blood pressure regulation by adjusting the blood volume. Next time we'll talk about some of the other medications and affecting how hard the heart works and the pipes resist. And we'll see some more about how why angiotensin II is such an important player.