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 mu g 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.