Influence of adrenodemedullation on beta 2- and beta 3-adrenoceptors mediating relaxation of oesophageal smooth muscle of spontaneously hypertensive rats

• Published in: British journal of pharmacology 1996-12, Vol.119 (7), p.1355-1360
• Main Authors: de Boer, R E, Steegstra, M R, Kroezen, P A, Smit, J, Zaagsma, J
• Format: Article
• Language: English
• Subjects: Adrenal Medulla - drug effects; Adrenal Medulla - physiology; Adrenalectomy; Adrenergic beta-Agonists - pharmacology; Adrenergic beta-Antagonists - pharmacology; Animals; Esophagus - drug effects; Esophagus - physiopathology; Ethanolamines - pharmacology; Fenoterol - pharmacology; Hypertension - genetics; Hypertension - physiopathology; In Vitro Techniques; Isoproterenol - pharmacology; Male; Muscle Relaxation - drug effects; Muscle, Smooth - drug effects; Muscle, Smooth - physiopathology; Propanolamines - pharmacology; Rats; Rats, Inbred SHR; Rats, Wistar; Receptors, Adrenergic, beta - drug effects; Receptors, Adrenergic, beta - physiology; Receptors, Adrenergic, beta-2 - drug effects; Receptors, Adrenergic, beta-2 - physiology; Receptors, Adrenergic, beta-3
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1111/j.1476-5381.1996.tb16046.x

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 preparations 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 microM, indicating only a minor contribution of beta 2-adrenoceptors. pA2-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 microM) 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 microM) now produced a clear rightward shift accompanied by a steepening of the CRC. A marked further shift was observed only at 100 microM 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 (pA2 = 5.11) was significantly different from the pA2 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 pEC50 value as well. 6. The results clearly indicate that beta 2-adrenoceptors in SHR oesophageal muscularis mucosae are desensitized, whereas beta 3-adrenoceptor-mediated responses are unaffected and similar to the responses observed in the Wistar rat oesophagus. The functional presence of beta 2-adrenoceptor-responses in SHR-ADM4 suggests a major role for adrenal-derived adrenaline in the desensitization of the beta 2-adrenoceptor-population.