Key result
30-day cold adaptation reduced functional sympatholysis in rabbits by increasing the number of pressor adrenergic receptors (Pm=312.5 vs 222.0 mm Hg, p<0.05), leading to greater arterial contraction to epinephrine.
Why the study?
Quantitative analysis of the pharmacokinetics and pharmacodynamics of epinephrine effects on arterial alpha-adrenergic receptors during functional sympatholysis before and during cold adaptation was lacking.
Does 30-day cold adaptation alter the reactivity of muscular arteries to epinephrine during functional sympatholysis in rabbits?
Does 30-day cold adaptation alter the reactivity of muscular arteries to epinephrine during functional sympatholysis in rabbits?
Cold adaptation increases the number of pressor adrenergic receptors, leading to greater epinephrine-induced arterial contraction during sympatholysis, which may serve as a survival mechanism to conserve heat.
Cold adaptation may alter epinephrine α-receptor reactivity in muscle arteries; leaves open effects on functional sympatholysis.
Background: Functional sympatholysis is determined as a tenfold increase in blood flow in the muscular arteries following the muscle contraction. This is explained by various mechanisms. However, there are no works on quantitative analysis of the pharmacokinetics and pharmacodynamics of the epinephrine effects on the arterial α-adrenergic receptors in sympatholysis before and during the cold adaptation. Aim: To study the effect of the 30-day cold adaptation on the adrenal reactivity of muscular arterial vessels to epinephrine in the functional sympatholysis. Material and methods: The experiments used four groups of rabbits. First group: control ( n =20); second group ( n =15): modelling of the muscle contraction by electrical stimulation in the sympatholysis; third group ( n =15): after 30-day cold adaptation; and fourth group ( n =15): modelling of the muscle contraction by electrical stimulation after 30-day cold adaptation. Adaptation to low temperatures was modeled at the daily 6-hour cooling at 10°C. A unique technique was used: blood was perfused into the limb muscles of all the rabbits via the femoral artery, after ligation of all anastomoses, using a constant flow pump. The adrenal reactivity was analyzed using the “dose-effect” response in double-reversed Lineweaver–Burk plot. This approach allowed determining the maximum pressor (Pm) response, which characterizes the number of active adrenergic receptors and the sensitivity (1/K) of the adrenergic receptors to epinephrine. Results: The sympatholysis was proved to be present in both the cold-adapted and control rabbits, but to a lesser extent. Sympatholysis reduced the contraction of arteries in response to epinephrine solely due to the mechanisms of the 24.49-fold reduced sensitivity of adrenergic receptors from 1/Km=1.2±6.7 1/μg.kg in the control group to 1/Km = 0.049±0.0016 1/μg.kg in the sympatholysis group ( p 0.05). The number of active adrenergic receptors did not significantly change (Pm=222.0 ±6.7 in the control group, Pm=222.0 ±7.5 in the sympatholysis group). As a process of arterial dilatation, sympatholysis reduced in the rabbits after the cold adaptation due to the increased number of the pressor adrenergic receptors in the cold conditions to Рm=312.5 ±11.0 mm Hg from Pm=222.0 ±7.5 mm Hg in the no-cold sympatholysis ( p 0.05). The sensitivity of adrenergic receptors to epinephrine (1/Km) in the no-cold sympatholysis and in the cold conditions did not significantly change ( p 0.05). Conclusion: Sympatholysis persists in the cold conditions but to a lesser extent than in the control group. As a stress hormone, epinephrine causes a greater contraction of arteries in the cold-adapted rabbits in sympatholysis than in no-cold conditions, which helps conserving heat in the body in such source of stress as the arctic cold, and improves survival.
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Ананьев et al. (2024) studied Healthy (experimental cold adaptation and sympatholysis model) (n=65). 30-day cold adaptation vs. No cold adaptation was evaluated on Maximum pressor response (Pm) characterizing the number of active adrenergic receptors during sympatholysis (p=<0.05). 30-day cold adaptation reduced functional sympatholysis in rabbits by increasing the number of pressor adrenergic receptors (Pm=312.5 vs 222.0 mm Hg, p<0.05), leading to greater arterial contraction to epinephrine.
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