INFLUENCE OF ADRENODEMEDULLATION ON BETA(2)-ADRENOCEPTOR AND BETA(3)-ADRENOCEPTOR MEDIATING RELAXATION OF ESOPHAGEAL SMOOTH-MUSCLE OF SPONTANEOUSLY HYPERTENSIVE RATS

1 In oesophageal smooth muscle strips from spontaneously hypertensive rats (SHR) of 8-10 and 22-24 weeks of age, respectively, beta-adrenoce ptor-mediated relaxation was investigated, by use of the beta-agonists , (-)-isoprenaline and fenoterol (both in the absence and presence of the beta(2)-selective antagonist ICI 118,551) and the selective beta(3 )-agonist, BRL 37,344. 2 In preparation from 8-10 week SHR, (-)-isopre naline- and fenoterol-induced concentration-response curves (CRCs) wer e hardly antagonized by ICI 118,551 at concentrations up to 1 mu M, in dicating only a minor contribution of beta(2)-adrenoceptors. pA(2)-val ues for ICI 118,551 of 5.30 ((-)-isoprenaline as agonist) and 5.46 (fe noterol as agonist), estimated from the shifts at the highest (10-100 mu M) antagonist concentrations, are consistent with affinity at a bet a(3)-adrenoceptor, similar to that in Wistar rat oesophageal smooth mu scle. 3 In 8-10 week SHR, adrenodemedullated at 4 weeks of age (SHR-AD M4) the potency of fenoterol was markedly increased and CRCs were shal low. In addition, ICI 118,551 (0.1 mu M) now produced a clear rightwar d shift accompanied by a steepening of the CRC. A marked further shift was observed only at 100 mu M of the antagonist. The data are compati ble with the involvement of both beta(2)- and beta(3)-adrenoceptors. 4 In 22-24 week animals, the same differences between SHR and SHR-ADM4 were observed with fenoterol as in 8-10 week animals, though beta-adre noceptor responsiveness was slightly decreased. The potency of ICI 118 ,551 at beta(3)-adrenoceptors (pA(2) = 5.11) was significantly differe nt from the pA(2) value of 5.46 obtained with the younger animals. 5 R esponses to the beta(3)-adrenoceptor agonist, BRL 37,344, were similar in Wistar rat and SHR preparations, In 8-10 week SHR, a small decreas e in the maximal response was observed, which in animals of 22-24 week s of age was accompanied by a small decrease in the pEC(50) value as w ell.