Summary
Positive inotropic responses to dobutamine have been examined using isolated myocardium from guinea pigs und humans. The potency (EC50) of dobutamine was 1.5 × 10−6 mol/l on guinea pig papillary muscles, 1.8 × 10−6 mol/l on guinea pig left atria and 2.5 × 10−6 mol/l on human papillary muscle strips. In guinea pig cardiac muscles, Schild plots for the β1-selective antagonist, 1-practolol, using dobutamine as agonist, had slopes of less than unity. This suggested the involvement of other receptors in the inotropic response to dobutamine. The β2-selective antagonist, ICI 118,551, but not the α1-selective antagonist, prazosin, attenuated the dobutamine response in guinea pig papillary muscles. Both ICI 118,551 and prazosin shifted the dobutamine concentration-response curve in guinea pig left atria. The positive inotropic response to dobutamine in human papillary muscles was antagonised by 1-practolol and ICI 118,551 but not by prazosin. The maximal inotropic response to dobutamine was 90% that of calcium measured in the same guinea pig papillary muscles but only 37% that of calcium in human papillary muscle strips. This reduced maximal effect of dobutamine in human myocardium is probably a disease-induced change but species variations cannot be excluded.
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References
Baumann G, Riess G, Erhardt WD, Felix SB, Ludwig L, Blümel G, Blömer H (1981) Impaired beta-adrenergic stimulation in the uninvolved ventricle post-acute myocardial infarction: Reversible defect due to excessive circulating catecholamine-induced decline in number and affinity of beta-receptors. Am Heart J 101:569–581
Bristow MR, Ginsburg R, Minobe W, Cubicciotti RS, Sageman WS, Lurie K, Billingham ME, Harrison DC, Stinson EB (1982) Decreased catecholamine sensitivity and β-adrenergic-receptor density in failing human hearts. N Engl J Med 307:205–211
Bristow MR, Kantrowitz NE, Ginsburg R, Fowler MB (1985) β-Adrenergic function in heart muscle disease and heart failure. J Mol Cell Cardiol 17 (Suppl 2):41–52
Brodde O-E (1982) Vascular dopamine receptors: demonstration and characterization by in vitro studies. Life Sci 31:289–306
Brown L, Erdmann E (1985) Concentration-response curves of positive inotropic agents before and after ouabain pretreatment. Cardiovasc Res 19:288–298
Brown L, Lorenz B, Erdmann E (1985) The inotropic effects of dopamine and its precursor levodopa on isolated human ventricular myocardium. Klin Wochenschr 63:1117–1123
Brown L, Lorenz B, Erdmann E (1986a) The positive inotropic effects of dopamine and dobutamine in isolated, contracting, diseased human and normal guinea pig ventricular myocardium. J Mol Cell Cardiol 18 (Suppl 1):306
Brown L, Lorenz B, Erdmann E (1986b) Reduced positive inotropic effects in diseased human ventricular myocardium. Cardiovasc Res 20:516–520
Brückner R, Meyer W, Mügge A, Schmitz W, Scholz H (1984) α-Adrenoceptor-mediated positive inotropic effect of phenylephrine in isolated human ventricular myocardium. Eur J Pharmacol 99: 345–347
Francis GS, Goldsmith SR, Cohn JN (1982) Relationship of exercise capacity to resting left ventricular performance and basal plasma norepinephrine levels in patients with congestive heart failure. Am Heart J 104:725–731
Ginsburg R, Bristow MR, Billingham ME, Stinson EB, Schroeder JS, Harrison DC (1983) Study of the normal and failing isolated human heart: Decreased response of failing heart to isoproterenol. Circulation 71:1023–1028
Goldberg LL, Glock D, Kohle JD, Barnett A (1984) Separation of peripheral dopamine receptors by a selective DA1 antagonist, SCH 23390. Hypertension 6 (Suppl 1):25–30
Kenakin TP (1981) An in vitro quantitative analysis of the alpha adrenoceptor partial agonist activity of dobutamine and its relevance to inotropic selectivity. J Pharmacol Exp Ther 216:210–219
Kenakin TP, Johnson SF (1985) The importance of the α-adrenoceptor agonist activity of dobutamine to inotropic selectivity in the anaesthetized cat. Eur J Pharmacol 111:347–354
Leier CV, Unverferth DV (1983) Dobutamine. Ann Int Med 99:490–496
Mügge A, Posselt D, Reimer U, Schmitz W, Scholz H (1985) Effects of the beta2-adrenoceptor agonists fenoterol and salbutamol on force of contraction in isolated human ventricular myocardium. Klin Wochenschr 63:26–31
Newman WH, Webb JG (1980) A differential inotropic responsiveness to isoprenaline and ouabain in dogs with heart failure. Cardiovasc Res 14:530–536
Ruffolo RR Jr, Spradlin TA, Pollock GD, Waddell JD, Murphy PJ (1981) Alpha and beta adrenergic effects of the stereoisomers of dobutamine. J Pharmacol Exp Ther 219:447–452
Ruffolo RR Jr, Yaden EL (1983) Vascular effects of the stereoisomers of dobutamine. J Pharmacol Exp Ther 224:46–50
Thomas JA, Marks BH (1978) Plasma norepinephrine in congestive heart failure. Am J Cardiol 41:233–243
Wagner J, Schümann HJ, Knorr A, Rohm N, Reidemeister JC (1980) Stimulation by adrenaline and dopamine but not by noradrenaline of myocardial α-adrenoceptors mediating positive inotropic effects in human atrial preparations. Naunyn-Schmiedeberg's Arch Pharmacol 312:99–102
Zerkowski H-R, Ikezono K, Rohm N, Reidemeister JC, Brodde OE (1986) Human myocardial β-adrenoceptors: demonstration of both β1- and β2-adrenoceptors mediating contractile responses to β-agonists on the isolated right atrium. Naunyn-Schmiedeberg's Arch Pharmacol 332:142–147
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These studies were supported by the Deutsche Forschungsgemeinschaft (Er 65/4-4). Part of these studies was presented at the XII Congress of the International Society for Heart Research in Melbourne, Australia, February 1986 (Brown et al. 1986a)
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Brown, L., Näbauer, M. & Erdmann, E. Dobutamine: positive inotropy by nonselective adrenoceptor agonism in isolated guinea pig and human myocardium. Naunyn-Schmiedeberg's Arch Pharmacol 335, 385–390 (1987). https://doi.org/10.1007/BF00165552
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DOI: https://doi.org/10.1007/BF00165552