A COMPARATIVE ANALYSIS OF THE PHARMACOKINETICS AND PHARMACODYNAMICS OF NOREPINEPHRINE AND EPINEPHRINE IN THEIR ACTION ON ARTERIES UNDER EXERCISE HYPEREMIA

Abstract

Aim. This paper aims to compare the pressor effects of norepinephrine and epinephrine on arterial adrenoceptors before and during exercise hyperemia. Materials and methods. The experiments were conducted in four series on rabbits. The first series (S1) was a norepinephrine control (n = 20), the second (S2) was norepinephrine under electrical muscle stimulation (n = 15), the third (S3) was an epinephrine control (n = 15), and the fourth (S4) was epinephrine under electrical stimulation (n = 15). In all rabbits, hindlimb muscles were perfused with their own blood through the femoral artery using a constant-flow pump. In all rabbits, arterial alpha-adrenoceptor activity was measured as the change in femoral perfusion pressure following administration of eight increasing doses of norepinephrine and epinephrine. Exercise hyperemia was modeled by electrical stimulation of the hindlimb muscles. Dose-response data were analyzed using Lineweaver–Burk double reciprocal plots, which allowed determination of alpha-adrenoceptor sensitivity to norepinephrine and epinephrine (1/К) and the number of active alpha-adreno­ceptors (Pm). Results. At all doses, the pressor effect of epinephrine was 29% greater than that of norepinephrine in the control series due to a greater number of active adrenoceptors (Pm) for epinephrine, with equal adrenoceptor sensitivity (1/K) to both epinephrine and norepinephrine. In exercise hyperemia conditions, the pressor effect of epinephrine exceeded that of norepinephrine due to a 40% greater adrenoceptor sensitivity (1/K) and a 29% greater number of active adrenoceptors (Pm) for epinephrine. Conclusion. The pressor effect of epinephrine on arteries was greater than that of norepinephrine, both in the control condition and during exercise hyperemia.