Response of the atrial pacemaker to dobutamine.

The action of dobutamine, (+/-)-4- [2- [[3-(p-hydroxyphenyl)-1-methylpropyl]amino]ethyl] pyrocatechol hydrochloride was studied on the pacemaker of the isolated rat atria. The dose-chronotropic response curve showed a typical bell-dome shape of the sympathomimetic amines. Reserpinization of the animals did not change the curve of the agonist. Cocaine (6.7 microgram/ml) induced a decrease of the sensitivity of the rat atria pacemaker for dobutamine (p less than 0.001). Propranolol (3 X 10(-8) and 10(-7) M) provoked a shift to the right of the dose-response curve for dobutamine. Also, the last concentration of the antagonist depressed the maxima (p less than 0.01). Phentolamine failed to prove a possible alpha-adrenergic action of the drug on the pacemaker. The response to dobutamine was not affected when monoaminoxidase was inhibited by pretreatment with pargyline, or when catechol-O-methyltransferase was inhibited by exposure to U-0521 (3,4 dihydroxy-alpha-methylpropiophenone). These results indicate that dobutamine: a) is a beta-adrenergic agent, b) is not a good substrate of MAO, c) is a direct-acting sympathomimetic amine.