CHRONOTROPIC AND INOTROPIC RESPONSES TO ADRENOCEPTOR AGONISTS INVITRO AFTER CHRONIC DOBUTAMINE TREATMENT IN THE RABBIT

1 Effects of long-term administration of the inotropic agent dobutamine (beta-and alpha-1-adrenoceptor agonist) on cardiac adrenoceptor function were studied in the rabbit. 2 After 2 weeks' continuous i.v. infusion of dobutamine (Dobutrex(R), 20-mu-g kg-1 min-1), spontaneous atrial rates in vitro were similar to controls, as were maximal rates in response to isoprenaline (262+/-17 vs 268+/-21 b.p.m., P>0.05) but the chronotropic potency of isoprenaline was reduced, as shown by a nine-fold increase in EC50. 3 Basal developed tension of papillary muscles was greater after chronic dobutamine treatment and increases in contraction force in response to beta-activation by isoprenaline and noradrenaline were significantly higher. Maximal developed tensions were 93+/-14% (P<0.02) and 94+/-25% (P<0.05) respectively greater than those of control muscles. 4 The inotropic potency of isoprenaline, but not noradrenaline, was reduced significantly after chronic dobutamine with a two-fold increase in EC50. 4 Responses to alpha-1-adrenoceptor activation by phenylephrine were unchanged after dobutamine treatment. 6 These changes are consistent with functional desensitization of the myocardium by the prolonged beta- but not alpha-1-agonist activity of dobutamine. In contrast, there was an enhanced effectiveness of beta-adrenoceptor activation.