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Low-Dose Adrenaline Reduces Blood Pressure Acutely in Anesthetized Pigs Through a β2-Adrenergic Pathway.

Journal of cardiovascular pharmacology (2019-07-06)
Anniek F Lubberding, Morten B Thomsen
ABSTRACT

Adrenaline (epinephrine) is one of the prime messengers of the fight-or-flight response, favoring the activation of β-adrenergic receptors. Although general vasoconstriction to nonessential tissues is imperative, the vasodilatory effect of β-adrenergic receptor activation contends with this. We aimed to determine the dose-dependent effects of adrenaline on hemodynamics and to test whether adrenaline could lower blood pressure (BP) through a β2-adrenergic pathway. Nineteen Danish landrace pigs were used to pharmacologically probe the hemodynamic effect of adrenaline. Pigs were anesthetized, intubated, and electrocardiogram, systolic BP (SBP), diastolic BP (DBP), and left ventricular pressure (LVP) were monitored continuously. First, we tested the dose-dependent effects of adrenaline (0.01-10 µg/kg). Second, we determined the response to adrenaline (0.3 µg/kg) after atropine, prazosin, and propranolol pretreatment. Finally, we tested the hemodynamic effect of salbutamol in a subset of pigs. All doses of adrenaline increased heart rate, while BP showed a biphasic response: At low doses, adrenaline decreased SBP from 118 ± 3 to 106 ± 4 mm Hg (n = 15; P < 0.05) and DBP from 86 ± 3 to 71 ± 3 (n = 15; P < 0.05), while at high doses, SBP and DBP increased. LVP showed a similar pattern, with a tendency of decreased pressure at low doses, and an increased pressure at high doses (P < 0.05). Pretreatment with autonomic blockers revealed that the increase in BP was due to α-adrenergic activity, while the decrease was due to β-adrenergic activity. In confirmation, β-adrenergic activation through salbutamol showed a similar decrease in SBP, DBP, and LVP. We conclude that adrenaline dose-dependently increases heart rate, while producing a biphasic response in BP with a decrease at low doses and an increase at high doses in an anesthetized, large-animal model.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Atropine sulfate salt monohydrate, ≥97% (TLC), crystalline
Sigma-Aldrich
Prazosin hydrochloride, ≥99.0% (HPLC)
Sigma-Aldrich
Salbutamol
Sigma-Aldrich
(±)-Propranolol hydrochloride, ≥99% (TLC), powder
Sigma-Aldrich
(−)-Epinephrine (+)-bitartrate salt, solid