The inotropic and chronotropic effects of catecholamines on the dog heart

Abstract

SUMMARY1. The chronotropic and inotropic responses of the denervated dog heart to intravenous infusions of noradrenaline, adrenaline and isoprenaline were studied.2. The maximum rate of rise of pressure in the left ventricle of the heart, (dP/dt max) measured at a constant heart rate and mean systemic arterial pressure during each series of infusions, was used as an index of inotropic changes (Furnival, Linden & Snow, 1970).3. The order of potency of the catecholamines in producing both chronotropic and inotropic effects was isoprenaline > adrenaline > noradrenaline.4. For the same increase in heart rate produced by an infusion of a catecholamine, noradrenaline caused a greater inotropic effect than adrenaline, which in turn caused a greater increase than isoprenaline.5. The chronotropic and inotropic effects of noradrenaline were potentiated by an intravenous injection of cocaine HCl (5 mg/kg), whereas those of isoprenaline were unchanged.6. The relative difference between the responses to noradrenaline and isoprenaline was abolished by an intravenous injection of cocaine HC1.7. It is concluded that the different relative chronotropic and inotropic effects of isoprenaline and noradrenaline are due to the greater uptake of noradrenaline by sympathetic nerve endings in the sinu-atrial node than in the muscle of the left ventricle.

THE CARDIOVASCULAR EFFECTS OF ICI 118,587: A β1‐ADRENOCEPTOR PARTIAL AGONIST

“…Firstly, quantitative measurements of the inotropic effects of compounds on the heart are technically difficult and of doubtful reliability when obtained in the presence of the large changes in heart rate and blood pressure which may be caused by doses of isoprenaline and noradrenaline (Furnival et al, 1970;Mason, Braunwald, Covell, Sonnenblick & Ross, 1971). However, previous experiments in carefully controlled preparations have shown that the same relative changes in force and rate are brought about by many compounds which act on the heart through the P-adrenoceptor (Furnival, Linden & Snow, 1971: Harry, Kappagoda, Linden & Snow, 1973Robie, Nutter, Moody& McNay, 1974;Bolter & Ledsome, 1976). In the present series of experiments it was shown that ICI 118,587 produced the same relative changes in the force of contraction for a given change in heart rate as did isoprenaline (Figure, 3).…”

The ACTIONS OF a NEW Β‐ADRENOCEPTOR BLOCKING DRUG, ICI 66082, ON THE RABBIT PAPILLARY MUSCLE AND ON THE DOG HEART

“…It has already been shown that the endogenous sympathomimetic amines in the blood stream in this dog preparation affect the myocardium (dP/dt max) but do not affect the sino-atrial node and this difference results from the greater uptake of catecholamines by the sympathetic nerves in the sino-atrial node than by those in the muscle (Furnival, Linden & Snow, 1971). Consequently, blockade of,-adrenoceptors in the heart in this preparation produces a reduction in dP/dt max but no change in heart rate (Harry et al, 1973).…”

Selectivity of Dobutamine for Adrenergic Receptor Subtypes

“…For example, Carlsson et al (32) observed in a reserpinized anesthetized cat model that the ratio ofthe drug dose required to produce a 50% maximal chronotropic response to the dose required to produce a 50% maximal inotropic response was 0.93 for the 8,-selective agonist (-) H80/60, 0.5 for the non-subtype selective agonist (-) isoproterenol, and 0.16 for the p32-selective agonist terbutaline. Other authors have reported proportionately greater effects upon heart rate than upon contractility from 82-selective, as opposed to non-subtype selective or /31-selective agents in other experimental preparations (33)(34)(35)(36)(37). induced by PGE1, which we observed in the presence of dobutamine, may reflect beta adrenergic agonist effects of dobutamine that are unopposed by a2-agonist effects.…”