During exercise, the heart is under natural stress and pumps blood faster through the blood vessels. As a result, blood flow sharply increases, and the filling of blood vessels also increases — a phenomenon called hyperemia. From the visual point of view, the excess of blood is realized as a change in skin color and local warming of the body area. Hyperemia can be stimulated, and nitric oxide (NO) and vasodilatory prostaglandins (PGs) are stimulators. The vascular action is limited to the activation of a soluble form of guanylate cyclase, which controls vascular wall tone and controls mitochondrial oxygen consumption. On the other hand, PGs dilate vascular walls, which helps to reduce resistance to blood flow and, consequently, lower blood pressure. In this study, both substances’ role was theorized to determine the possibilities of their inhibition to study the effect on hyperemia. It was determined that NO and PGs contribute significantly to hyperemia, with independent effects.
Ideally, the use of NO and PG inhibitors should affect hyperemia primarily by causing vasoconstriction of the vessel walls to normalize. However, vasoconstriction should increase resistance and consequently decrease blood flow. Then at least three options should be investigated: NO inhibition, PGs inhibition, and combined inhibition. These were the objectives of the study.
If continue this thought, according to the authors, the use of inhibitors of NO and PGs synthesis can significantly affect the intensity of hyperemia processes. In particular, the use of L-NAME was aimed at inhibiting NO synthesis. The authors used Ketorolac to inhibit PGs (in particular, COX was used). The use in specific sequences, as will be shown later, was aimed at studying the dynamics of hyperemia.
Research Question, Hypothesis, Purpose
Thus, in the present experiment, it is advisable to distinguish several aspects. Firstly, it is the use of inhibitor drugs. Secondly, these are substances that dilate the vessels, which probably stimulates hyperemia. Thirdly, it is the use of sensors to recognize blood flow velocity as evidence of changes.
The methodological basis of this experiment consisted of five conditional phases. During the first phase, a sample of 14 individuals was collected; to prevent systematic error, each individual had to be healthy, not pregnant, and without menstrual cycles at the time of testing. In the second phase, each respondent was connected to a brachial catheter with an FBF blood flow sensor proximal to the end of the catheter. In the third phase, inhibitors were administered through the catheter according to two schemes – firstly, it was a sequential injection of L-NAME and Ketorolac with evaluation immediately after each injection, and secondly, it was an injection of a joint mixture to study the effects of the combined therapy. In the end, mean arterial pressure and HR data were collected as a waveform for each respondent. The data were then processed automatically using statistical software.
Methodology: The Third Phase
Let us elaborate on the third phase of the methodology because it is one of the central manipulations of the entire experiment. The figure on the slide reflects the two schemes of the experiment, A and B; the difference between them is precisely how the inhibitor drugs are administered. During the first phase, after a short rest, the respondents proceeded to a 20-minute training session (the training procedure was implemented using light-sound signals, so its reliability is beyond doubt). For the first five minutes, the physiological solution was injected into the vessel through the catheter to prepare the vessel, and after this time, the L-NAME injection was started. Recall, L-NAME was used to inhibit NO synthesis, and the dynamics of hyperemia were recorded. This was followed again by a saline stage (relaxation), after which Ketorolac (a PGs inhibitor) was injected into the respondent’s bloodstream for five minutes (hyperemia dynamics were recorded). This was followed by recovery with saline.
The second regimen was used as combination therapy. After some recovery time, a mixture of L-NAME and Ketorolac was injected into the vessel using a brachial catheter, followed by the recovery phase. Remarkably, only eight out of 14 respondents were invited to this regimen.
Results (1 Scheme)
Let us look at the results carefully. At first glance, the table seems confusing, but it is quite informative. The table presents data on arterial diameter, heart rate, mean arterial pressure, and other characteristics, but it is the ones described that take precedence. It can be seen that neither heart rate nor blood pressure changed significantly from the starting point to the endpoint for the first scheme (marked in red). The graph shows the dynamics of FBF as a function of time for the first training group. It can be well seen that the tracer FBF decreased after sequential administration, from which we can conclude that both L-NAME and Ketorolac (Ketorolac in particular) reduce the dynamics of hyperemia. This change is moderate.
Results (2 Scheme)
During the combined therapy, the changes were also moderate, but it was noticeable that FBF significantly decreased both at rest and during exercise (as shown in the graph). From this, it was concluded that the combined therapy had a significant effect on both changes in hyperemia, in contrast to the sequential administration of inhibitors.
Hyperemia is a condition in which blood vessels fill by intensifying the work of the heart muscle. It is a normal response, allowing oxygen to move faster through the tissues to prevent hypoxia. This experiment evaluated the extent to which the use of NO and COX inhibitors can control hyperemia. Both NO and COX are vasodilators that increase blood flow and therefore promote hyperemia; their inhibition should then have the opposite effect. Two regimens were evaluated – sequential and combined administration of inhibitors of each type.
Schrage, W. G., Joyner, M. J., & Dinenno, F. A. (2004). Local inhibition of nitric oxide and prostaglandins independently reduces forearm exercise hyperaemia in humans. The Journal of physiology, 557(2), 599-611.