Influence of adrenodemedullation on β2‐ and β3‐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: Boer, Robert E.P., Steegstra, Mathijs R., Kroezen, Peter A., Smit, Jenneke, Zaagsma, Johan
• Format: Article
• Language: English
• Subjects: adrenal demedullation; Arterial hypertension. Arterial hypotension; Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Experimental diseases; Medical sciences; rat oesophagus; SHR; β2‐ and β3‐adrenoceptors; β‐adrenoceptor desensitization
• 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, β‐adrenoceptor‐mediated relaxation was investigated, by use of the β‐agonists, (—)‐isoprenaline and fenoterol (both in the absence and presence of the β2‐selective antagonist ICI 118,551) and the selective β‐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 μm, indicating only a minor contribution of β2‐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 μm) antagonist concentrations, are consistent with affinity at a β3‐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 μm) now produced a clear rightward shift accompanied by a steepening of the CRC. A marked further shift was observed only at 100 μm of the antagonist. The data are compatible with the involvement of both β2‐ and β3‐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 β‐adrenoceptor responsiveness was slightly decreased. The potency of ICI 118,551 at β3‐adrenoceptors (pA2 = 5.11) was significantly different from the pA2 value of 5.46 obtained with the younger animals. 5 Responses to the β3‐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 β2‐adrenoceptors in SHR oesophageal muscularis mucosae are desensitized, whereas bT3‐adrenoceptor‐mediated responses are unaffected and similar to the responses observed in the Wistar rat oesophagus. The functional presence of bβ2‐adrenoceptor‐responses in SHR‐ADM4 suggests a major role for adrenal‐derived adrenaline in the desensitization of the β2‐adrenoceptor‐population.