In our previous blog miniseries “Experimental Puzzles”, specific publications were used as examples of how to design an experimental approach to answer your research question, especially when studying complex regulatory mechanisms in vivo.

In this new series, we invite the reader to explore the physiological aspects of a research model and some of the cardiovascular mechanisms addressed in the previous series. Although each of these blogs can be read as independent pieces, the “series format” allows us to focus on specific features while providing incremental information. This series will discuss cardiovascular reflexes, specifically regulating different regional blood flows under physiological and pathophysiological conditions.

Here we will review the publication “Muscle metaboreflex activation during dynamic exercise evokes epinephrine release resulting in β2-mediated vasodilation” which is freely available. We recommend you download the paper to accompany reading this blog.

Background and Rationale

1. Muscle metaboreflex is activated by increased O₂ demand and metabolite accumulation in the exercising musculature (active ischemic muscle).
2. The metaboreflex mechanism increases Heart Rate (HR), Cardiac Output (CO), ventricular contractility and blood pressure; all aimed to restore adequate O₂ supply to the active ischemic muscle.
3. Muscle metaboreflex activation seems to also increase sympathetic activity and peripheral vasoconstriction.
4. The reflexive increase in the sympathetic activity promotes adrenal gland epinephrine release, which can elicit substantial vasodilation, especially in the skeletal muscle (ischemic or not).
5. The Cardiac Output (CO) response increases blood pressure, improving blood flow to the active ischemic muscle. This increase in blood pressure is not due to a systemic vasoconstriction. In fact, systemic vasodynamic activity leans towards epinephrine/vascular β2-receptors mediated vasodilation.
6. The metaboreflex however seems to promote both vasodilation and vasoconstriction in different vascular beds (systemic peripheral; ischemic vs. non-ischemic)
7. The study evaluates if epinephrine released during metaboreflex activation causes β2-mediated peripheral vasodilation.

Methodology

Using a similar design to what we saw in Experimental Puzzles 1), this study describes the strategic instrumentation of mongrel canines that were used to independently evaluate the vasoactivity of systemic and regional blood flows.

1. A transit-time ultrasound flow probe placed around the ascending aorta provided Cardiac Output (CO).
2. A transit-time ultrasound flow probe placed around the abdominal aorta provided direct information regarding hindlimbs blood flow, which is directly related to the muscle metaboreflex activation via ischemia. This ischemia was induced by gradual occlusion of the abdominal aorta (by occluders) during treadmill exercise.
3. Blood pressure data (measured directly from a catheter placed in the abdominal aorta), combined with blood flow data, provides a vasoactivity index expressed, in this case, as conductance (calculated as blood flow divided by blood pressure).
   1. Once the muscle metaboreflex is activated by partial inflation of terminal aortic occluders during moderate treadmill exercise, the hindlimb blood flow can be described as ischemic vasculature.
   2. The assessment of the non-ischemic vasculature is then calculated as CO (total blood flow) minus the abdominal aorta blood flow (ischemic vasculature). Again, the availability of blood pressure data allows for vascular conductance calculation for the non-ischemic vasculature.
4. Experimental procedures: The muscle metaboreflex activation protocol was performed, and blood samples were collected for epinephrine level analysis, under the following conditions:
   1. Control
   2. β-adrenergic blockade (propranolol)
   3. α1-adrenergic blockade (prazosin),
   4. α1 + β blockade.

Results and Discussion Highlights

1. Activation of the muscle metaboreflex increased plasma epinephrine levels (see publication figure # 2).
2. β-blockade decreased the conductance on the non-ischemic vasculature (publication figure # 3) when compared to control conditions, indicating that the epinephrine release promoted β2-mediated vasodilation.
3. The α1-blocklade decreased the arterial pressure and increased the non-ischemic vasculature conductance (see publication figure # 3), revealing a potential α-adrenergic mediated vasoconstriction on the active skeletal muscle under control conditions (see publication figure # 3).
4. The α1-blocklade + β-blockade showed a decreased non-ischemic vascular conductance when compared to control conditions, revealing a potential larger β2-mediated vasodilation contribution in the balance between α-adrenergic mediated vasoconstriction and β2-mediated vasodilation (see publication figure # 3).

The results shown in this publication demonstrate that increased epinephrine release, opposes α-mediated vasoconstriction via β2-mediated vasodilation, therefore improving blood flow to the ischemic active skeletal muscle.

We hope that this blog will entice you, our readers, as we continue to discuss metaboreflex mechanisms. Also, we invite you to attend our upcoming free live webinar featuring the author of this paper, Dr. Kaur. During this webinar, you can ask Dr. Kaur questions about this study, its design, and ultimate conclusions. To view our past and future webinars, please click here.