THE BETA-ADRENOCEPTOR SELECTIVITY PROFILE OF BRL-37344 IN THE PITHED RAT

1 Rats were pithed in order to disrupt baroreflex pathways. Heart rate was used as a measure of beta(1)-adrenoceptor activity, blood pressur e as a measure of beta(2)-adrenoceptor activity and oxygen consumption and brown adipose tissue temperature as measures of beta(3)-adrenocep tor activity. 2 The effects of the selective beta(3)-adrenoceptor agon ist BRL 37344 were compared with those of isoprenaline, a non-selectiv e beta-adrenoceptor agonist, and denopamine and salbutamol, which are respectively beta(1) and beta(2)-adrenoceptor agonists. 3 Denopamine w as 10-fold more potent on heart rate than blood pressure, whilst salbu tamol was 18-fold more potent on blood pressure than heart rate. These findings confirm that in this preparation increases in heart rate are predominantly beta(1) adrenoceptor-mediated, whilst blood pressure is beta(2)-adrenoceptor-mediated. Further confirmation is provide beta 2 -adrenoceptor-mediated. Further confirmation is provided by the blocka de with atenolol, of the chronotropic effect, but not the blood pressu re effect, of isoprenaline. 4 BRL 37344 was the most potent beta-adren oceptor agonist on both oxygen consumption and brown adipose tissue te mperature, revealing the beta(3)-nature of these responses. Dose-respo nse curves for oxygen consumption and brown adipose tissue temperature were identical, whichever of the beta-adrenoceptor agonists was used. Both systems may be considered equally effective as indicators of bet a(3)-adrenoceptor agonist activity.