As you may remember from our lesson on aging, one of the complications associated with aging is hypertension, which induces vascular dysfunction. What we have here today is one of the most widely established machines to study vascular function in basic research. And indeed, this is called an organ chamber myograph. And, as the name itself suggests, myograph is able to read and record muscle strength, in particular here, the muscles eliciting vasoconstriction and vasorelaxation and translate it into a graph. So, in a typical experimental setting, we would have different animals with different diseases, and we would isolate relevant arteries from these animals, such as, for instance, the aorta. So, in a typical case scenario, we would have a hypertensive mouse versus a non-hypertensive mouse or a hypertensive mouse versus a hypertensive mouse treated with an experimental drug. Once the artery of interest is isolated, it will then be cut into smaller rings, and each ring will, in turn, be mounted inside wells belonging into the organ chamber. As you can see, inside each well, there are two small needles. And each aortic ring is then slid on to these two needles, and later through this micro manipulator, it is adjusted to its resting tension. Then each chamber in the corresponding well will be placed back onto the station and filled with the physiological buffer. At this point, we will then have several rings from one animal and several rings from the other animal, so as to be able to compare vascular function in terms of relaxation as well as constriction into different disease types or treatment strategies. And amongst the several agonists that we are used to elicit vasorelaxation, perhaps the most established is acetylcholine, which induces vasorelaxation of the aorta in this case. Ultimately, what we end up with after this experiment is a graph such as the one you see here. What we have on the x-axis is increasing concentrations of acetylcholine, which is the agonist we use to elicit vasorelaxation. While on the y-axis, we have an increased percentage of relaxation, as compared to the baseline. And as you may notice, we see that with increasing concentrations of acetylcholine, the percentage of relaxation increases up until reaching 100%, which is maximum relaxation. And we are usually then faced with several experiments comparing arteries originating from different animals, which have been treated with different therapeutic principles or that have different disease models. In this case, you see two curves, one is the one with the black circles, which we have just discussed. And another one on top of it, is with white circles. And the second curve on top denotes a shift towards the right and a decrease, a blunting in the maximal response to acetylcholine. So, as you can see, the maximal response in the baseline animal is 100% with a full relaxation, while in the second artery originating from the different animal, is reaching a maximum relaxation of 70%. This denotes the fact that somehow the function of this vessel is blunted, and this is depicted by the fact that at each concentration of acetylcholine, the response is decreased throughout the curve as well as the maximum relaxation. And what we can also do with such a machine, and this is why we have several different repeats of the same artery, is to use different pharmacologic inhibitors. So as to elucidate exactly how each condition is represented in the disease model of the animal acts on to the vascular bed, causing dysfunction or improvements in the dysfunction. And this is a machine that has enabled us to study several genes and to understand how different diseases encountered with aging cause vascular dysfunction. And certainly, also in the setting of hypertension, this machine, organ chamber myograph, has proven crucial for the studying of these settings. Thank you very much for your attention.
