Effect of chemical sympathectomy on (-)-isoprenaline-induced changes in cardiac beta-adrenoceptor subtypes in the guinea-pig and rat.

1. Quantitative autoradiography was used to determine beta-adrenoceptor densities in cardiac regions of guinea-pigs and rats after chemical sympathectomy with 6-hydroxydopamine, and to examine how chemical sympathectomy affected beta-adrenoceptor changes following infusion of (-)-isoprenaline (400 micrograms kg-1 hr-1, 7 days). 2. Seven days after 6-hydroxydopamine (100 mg kg-1, i.v.), cardiac tissue levels of noradrenaline were reduced by 94.0 +/- 3.5% (guinea-pig) and 86.0 +/- 7.0% (rat). The blood pressure increase in rats to tyramine (0.5 mg, i.v.) was reduced from 118 mmHg in controls to 4.4 mmHg in 6-hydroxydopamine-treated animals. 3. There were no changes 7 and 14 days after 6-hydroxydopamine treatment in total, beta 1-and beta 2-adrenoceptor density in the atrioventricular conducting system and atrial and ventricular myocardium in both species. 4. In control animals, (-)-isoprenaline infusion produced selective reductions in beta 2-adrenoceptor density, whilst beta 1-adrenoceptor density remained unchanged. 5. In 6-hydroxydopamine treated guinea-pigs or rats, (-)-isoprenaline infusion caused no change in beta 1-adrenoceptors except in the right bundle branch whilst beta 2-adrenoceptors were reduced in the atrioventricular conducting system (atrioventricular node, bundle of His, right and left bundle branches) and myocardium (interventricular septum and atria). 6. The differential effect of (-)-isoprenaline on beta 1- and beta 2-adrenoceptors is not therefore due to the occupation of beta 1-adrenoceptors by noradrenaline or to prior down-regulation of beta 1-adrenoceptors by noradrenaline, since it persists after depletion of noradrenaline.