Dobutamine: positive inotropy by nonselective adrenoceptor agonism in isolated guinea pig and human myocardium

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Abstract
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.