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Influence of beta adrenoceptor blockade by metoprolol and propranolol on plasma concentrations and effects of noradrenaline and adrenaline during intra venous infusion

Influence of beta adrenoceptor blockade by metoprolol and propranolol on plasma concentrations and effects of noradrenaline and adrenaline during intra venous infusion

Acta Physiologica Scandinavica Suppl. (515): 45-54

To study the concentration-dependence of responses to circulating noradrenaline (NA) [norepinephrine] and adrenaline (ADR) [epinephrine], 6 healthy volunteers received graded i.v. infusions of NA and ADR in a single-blind study. Venous plasma NA was increased step-wise from 1.44 .+-. 0.22 to 12.24 .+-. 2.47 nM and ADR from 0.28 .+-. 0.10 to 4.05 .+-. 0.67 nM. NA increased systolic and diastolic blood pressures (SBP and DBP) and reduced heart rate (HR) at about 6 nM in venous plasma. ADR decreased DBP concentration-dependently, but increased SBP and HR only at 4 nM. ADR increased plasma cAMP significantly at 0.7 nM. Increases in subjective ratings of discomfort were obtained at 1.9-4 nM ADR and 12 nM NA in plasma. The subjective effects of ADR were counteracted by propranolol but not by the .beta.1-selective antagonist metoprolol, whereas both blockers tended to reduce responses to NA. Metoprolol enhanced NA and ADR concentrations during infusions by 65-75% at the highest infusion rates. Propranolol enhanced ADR levels considerably more than NA levels (by 189 and 75%, respectively, at the highest infusion rates). The 2 .beta.-blockers reduced resting HR and SBP but not DBP or cAMP. Responses to NA were similar during .beta.-blockade. Metoprolol did not influence the plasma cAMP response to ADR but attenuated the DBP reduction. HR remained unchanged. Propranolol antagonized the plasma cAMP response to ADR markedly and caused ADR to increase DBP and decrease HR. Both NA and ADR may act as circulating hormones, and differences in the response pattern may be related to the .beta.-agonist properties of ADR. Caution should be exerted when evaluating sympatho-adrenal activity by plasma catecholamine measurements since .beta.-blockade alters catecholamine kinetics in plasma and since this effect varies with different .beta.-blockers.

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Accession: 005681009

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Influence of beta-adrenoceptor blockade by metoprolol and propranolol on plasma concentrations and effects of noradrenaline and adrenaline during i.v. infusion. Acta Physiologica Scandinavica. Supplementum 515: 45-53, 1983

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