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

Positive inotropic responses to dobutamine have been examined using isolated myocardium from guinea pigs und humans. The potency (EC50) of dobutamine was 1.5 X 10(-6) mol/l on guinea pig papillary muscles, 1.8 X 10(-6) mol/l on guinea pig left atria and 2.5 X 10(-6) mol/l on human papillary muscle strips. In guinea pig cardiac muscles, Schild plots for the beta 1-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 beta 2-selective antagonist, ICI 118,551, but not the alpha 1-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 l-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.