Local Factors of Arterial Pressure – Blood Vessels and Pressure

00:00 So now let's take a little bit of break from the neurohormonal factors and the vascular anatomy and let's focus on the local factors that control systemic vascular resistance. Because again what are the key points for controlling mean arterial pressure? Cardiac output times systemic vascular resistance. So let's talk about the local factors that affect systemic vascular resistance. In these local factors, there are quite a few, some of them will cause dilation or relaxation of a blood vessel and some will cause constriction of the blood vessel. So a dilation of course is going to open that vessel up and a constriction is going to decrease it. Those two things will change the radius of the blood vessel which then changes its resistance because again radius of the blood vessel is raised to the fourth power and thus is so important for overall resistance. You can see here there's a couple of very important items to think about with the local control of a blood vessel.

01:16 Nitric oxide can do this by a two distinct mechanisms.

01:20 Let's start off with the most common.

01:22 And that is acetylcholine being released from a presynaptic nerve terminal.

01:28 This then binds to a postsynaptic muscarinic receptor on the endothelial cell.

01:34 This endothelial cell has these muscarinic receptors which are G protein-coupled receptors, releasing IP3.

01:42 IP3 then causes the release of calcium from the endoplasmic reticulum.

01:48 Calcium activates a very special enzyme.

01:51 In this case, it's endothelial nitric oxide synthase.

01:56 This endothelial nitric oixide synthase known as eNOS then allows the production of nitric oxide.

02:02 Nitric oxide is a gas that will diffuse across the endothelial layer out into the interstitial space and to the smooth muscle.

02:12 It enters the smooth muscle, it stimulates another enzymes, guanylyl cyclase, and that produces cyclic GMP which causes relaxation of the smooth muscle, which causes vasodilation.

02:28 the other way in which you can get nitric oxide release is through the nerve itself.

02:35 There's a special enzyme known as neuronal nitric oxide synthase that also can produce nitric oxide.

02:42 The gas in the presynaptic terminal.

02:45 It is done through L-arginine, is the substrate.

02:49 Nitric oxide is the product of nNOS.

02:53 This again diffuses across the synaptic space into the smooth muscle, activates guanylyl cyclase producing cyclic GMP which again causes smooth muscle relaxation and vasodilation.

03:11 So whether you get it through nNOS which is directly nitric oxide release from the nerve or through the more traditional route in which endothelial cells, eNOS produces the nitric oxide to cause smooth muscle relaxation.

03:28 Now there are a number of factors that affect either nitric oxide or calcium levels.

03:36 So let's go through a few of those now.

03:38 Prostaglandins and endothelial-derived hyperpolarizing factor directly affect calcium levels.

03:48 Those two items will cause there to be a relaxation because of decrease in calcium levels.

03:54 Interestingly, even things like shear stress, which is the amount of stress across the endothelial wall will cause nitric oxide to be released which decreases the calcium within the smooth muscle cells.

04:11 Other items that become very important are things like bradykinin, substance P, ATP and even acetylcholine are all vasodilatory molecules that cause this relaxation of the smooth muscle and these are important processes to think about when we're trying to derive a physiological effect of vascular resistance.

04:40 The last item I will bring up is that in certain toxins will also cause a vasodilation and this is denoted by oftentimes bacterial endotoxins will cause increases in both nitric oxide and decreases in calcium levels.

04:58 So now let's go from the dilation relaxation portion and talk about contraction of the smooth muscle cell.

05:08 There are less items to be concerned with here but let's go to the big mechanisms.

05:14 One of the big mechanisms is an increase in endothelins and the second is you need to get an increase in calcium within the smooth muscle to cause a constriction or contraction.

05:28 What other things become important? Well, we've already talked about a few of these.

05:34 One is angiotensin II.

05:36 Angiotensin II interacts with the endothelium to cause an increase in smooth muscle calcium.

05:46 There are other molecules that are also related to prostaglandins called thromboxanes that will also increase the smooth muscle calcium levels. Besides molecules, there are even things like trauma that can cause this response to occur. So if you have trauma within a blood vessel, that will oftentimes decrease the amount of blood flow within the vessel because of causing an active contraction or constriction.

06:18 Remember any time you decrease the luminal diameter of the vessel, you increase its resistance and therefore decrease blood flow.