Abstract
Catecholamines (isoproterenol, norepinephrine, methoxamine) have an effect on the force-interval relationship (FIR) (the way the force of contraction depends on the rate and pattern of stimulation) which is unique among inotropic agents. Although the effect on the FIR of a low dose of isoproterenol (10−8M) is similar to that of other agents (e.g. elevation of calcium concentration), intermediate doses (10−7, 10−6M) cause the curves that characterize the FIR (monophasic for the control and the low dose) to become biphasic; large doses (10−5M) strikingly accentuate this effect turning post-extrasystolic potentiation into post-extrasystolic depression. Propranolol (10−7M) and practolol (10−6M) blocked these effects competitively whereas phentolamine (5 × 10−6M) and isopropylmethoxamine (5 × 10−6M) did not. Thus, the effect of changing the FIR from a monophasic to a biphasic function can be deemed a β1 action, unrelated to α or β2 sites. Norepinephrine (10−7, 10−6, and 10−5M) produced the same results. Methoxamine (10−3, 10−4M), not usually considered a β agonist, also produced this same effect on the FIR. These results demonstrate the potential usefulness of the FIR as a means of identifying and classifying inotropic agents as well as providing a method of analysis for testing hypotheses concerning the mode of action of β1 agonists.
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Anderson, P., Manring, A. & Johnson, E. CATECHOLAMINE EFFECT ON THE FORCE-INTERVAL RELATIONSHIP. Pediatr Res 11, 386 (1977). https://doi.org/10.1203/00006450-197704000-00099
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DOI: https://doi.org/10.1203/00006450-197704000-00099
