Chronotropic and inotropic responses to adrenoceptor agonists in vitro 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, 20 micrograms 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 greater than 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 less than 0.02) and 94 +/- 25% (P less than 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. 5. 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.
Brown
M D
MD
Department of Physiology, University of Birmingham Medical School, UK.
D000818:Animals; D004280:Dobutamine / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006339:Heart Rate / Q000187:drug effects*; D066298:In Vitro Techniques; D007262:Infusions, Intravenous; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D011817:Rabbits; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D013268:Stimulation, Chemical
D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D004280:Dobutamine; D007545:Isoproterenol; D009638:Norepinephrine