Influence of adrenodemedullation on beta(2)- and beta(3)-adrenoceptors mediating relaxation of oesophageal 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-adrenoceptor-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, (-)-isoprenaline- and fenoterol-induced concentration-response curves (CRCs) were hardly antagonized by ICI 118,551 at concentrations up to 1 mu M, indicating only a minor contribution of beta(2)-adrenoceptors. pA(2)-values for ICI 118,551 of 5.30 ((-)-isoprenaline as agonist) and 5.46 (fenoterol as agonist), estimated from the shifts at the highest (10-100 mu M) antagonist concentrations, are consistent with affinity at a beta(3)-adrenoceptor, similar to that in Wistar rat oesophageal smooth muscle. 3 In 8-10 week SHR, adrenodemedullated at 4 weeks of age (SHR-ADM4) the potency of fenoterol was markedly increased and CRCs were shallow. In addition, ICI 118,551 (0.1 mu M) now produced a clear rightward 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 compatible 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-adrenoceptor responsiveness was slightly decreased. The potency of ICI 118,551 at beta(3)-adrenoceptors (pA(2) = 5.11) was significantly different from the pA(2) value of 5.46 obtained with the younger animals. 5 Responses to the beta(3)-adrenoceptor agonist, BRL 37,344, were similar in Wistar rat and SHR preparations, In 8-10 week SHR, a small decrease in the maximal response was observed, which in animals of 22-24 weeks of age was accompanied by a small decrease in the pEC(50) value as well.