Adrenergic receptor mechanisms of functional sympatholysis in the regulation of regional blood flow in response to epinephrine after 5-day cold acclimation

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Abstract

BACKGROUND:. During muscle contraction, blood flow in the working muscles increases tens of times due to the mechanisms of sympatholysis. However, there are no studies that would quantitatively describe the effect of epinephrine on arterial alpha-adrenergic receptors during sympatholysis against the background of 5-day cold adaptation.

AIM: Objective. To study the effect of five-day cold adaptation on the adrenoreactivity of muscle arterial vessels during sympatholysis to different doses of epinephrine.

MATERIAL AND METHODS: Material and methods. The experiments were carried out in 4 groups of rabbits. Control group (N1, n = 20) of rabbits. Sympatholysis group (N2, n = 15): electrical stimulation of muscles (frequency 5 Hz, voltage 10 V, L = 5 ms) to induce sympatholysis. Cold adaptation group (N3, n = 15) after 5-day exposure in a climatic chamber (−10 ° C, 6 h / day). Group (N4, n=15): combination of 5 days of cold adaptation with sympatholysis. In all rabbits, the limb muscles were perfused with blood through the femoral artery after ligation of all anastomoses using a constant-flow pump. After the introduction of 8 doses of epinephrine (0.5–30 μg/kg), the adrenoreactivity of the limb arteries was analyzed using the dose-effect reaction in double inverse Lineweaver–Burk coordinates. This allowed us to determine the number of active adrenoreceptors (Pm) and the sensitivity (1/Km) of adrenoreceptors to epinephrine.

RESULTS:  Sympatholysis after 5 days of cold adaptation (N4) was much less for all doses of epinephrine than without cold (N2), which proved a decrease in blood flow in the working muscles during sympatholysis against the background of cold. Analysis of this mechanism in double inverse Lineuwer-Burk coordinates revealed an increase in the number of active a-ARs (by 1.407 times or 40.7%) to Pm=312.5 mmHg during sympatholysis after cold with Pm=222 mmHg during sympatholysis without cold. At the same time, after cold (N4) during sympatholysis, the sensitivity (1/Km) of alpha-adrenoreceptors to epinephrine increased by 1.632 times (by 63.2%) to 1/Km=0.08 from the value of 1/Km=0.049 during sympatholysis without cold (N2). Complete leveling of sympatholysis after cold with 30 μg/kg epinephrine confirms the critical role of dose-dependent pharmacokinetics of arterial tone regulation under cold stress conditions.

CONCLUSION: Conclusion. The obtained data allow us to draw the following conclusion: sympatholysis against the background of 5 days of cold persists, but was less than sympatholysis without cold. Increased adrenergic vasoconstriction after 5 days of cold optimizes heat conservation, but reduces blood flow in the working muscles, which limits physical performance. The discovered mechanisms explain the phenomenon of "early cold asthenia" in individuals with short-term arctic exposure, characterized by a decrease in tolerance to physical activity while maintaining basic hemodynamic homeostasis.

About the authors

Vladimir N. Ananev

Institute of Biomedical Problems of the Russian Academy of Sciences

Author for correspondence.
Email: noradrenalin1952@mail.ru
ORCID iD: 0000-0002-4679-6441
SPIN-code: 1718-8446

MD, Dr. Sci. (Medicine), Professor

Russian Federation, Moscow

Georgy V. Ananev

Pharmstandard JSC

Email: gvananiev@pharmstd.ru
ORCID iD: 0009-0005-4287-8430
SPIN-code: 4845-8340
Russian Federation, Moscow

Vladimir I. Torshin

Peoples’ Friendship University of Russia

Email: vtorshin@mail.ru
ORCID iD: 0000-0002-3950-8296
SPIN-code: 8602-3159

Dr. Sci. (Biology), Professor

Russian Federation, Moscow

Olga V. Ananeva

Tyumen State Medical University

Email: olvasan@mail.ru
ORCID iD: 0000-0002-0672-9164
SPIN-code: 1239-5484

MD, Dr. Sci. (Medicine), Professor

Russian Federation, Tyumen

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2. Fig. 1. Increase in perfusion pressure in the femoral artery across four rabbit groups in response to eight doses of epinephrine: control group (N1), sympatholysis (N2), after 5-day cold acclimation (N3), and sympatholysis after 5-day cold acclimation (N4). X-axis: epinephrine dose (µg/kg); Y-axis: increase in perfusion pressure (mmHg). All differences between the sympatholysis group (N2) and the control group (N1) were statistically significant (p < 0.01). All differences between the group with sympatholysis after 5-day cold exposure (N4) and the 5-day cold exposure group (N3) were statistically significant (p < 0.01). Experimental data for the group with sympatholysis after 5-day cold exposure (N4) and the sympatholysis group (N2) were statistically significant (p < 0.05). The epinephrine response at 0.5 µg/kg in groups N3 and N1 was not statistically significant (p > 0.05). The epinephrine response at 30 µg/kg in groups N4 and N1 was not statistically significant (p > 0.05).

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3. Fig. 2. Increase in perfusion pressure in the femoral artery across four rabbit groups in response to eight doses of epinephrine: control group (N1), sympatholysis (N2), after 5-day cold acclimation (N3), and sympatholysis after 5-day cold acclimation (N4), shown in double reciprocal Lineweaver–Burk coordinates. X-axis: inverse dose of epinephrine, 1/(µg/kg). Y-axis: inverse perfusion pressure, 1/(mm Hg).

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