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Endothelin-1 induced a unusual transient biphasic effect (relaxation followed by contraction) in the isolated guinea-pig ileum. The contractile component of the response was concentration-dependent in the dose range studied, but the relaxant component was not. Neuronal mechanisms and cyclic GMP do not seem to be involved in the relaxing effect since this component was not affected by either tetrodotoxin, atropine or methylene blue. Endothelin-1 induced desensitization which was well characterized for the contractile component of the response, and was only partially reversed after a 3-h resting period. The effects of endothelin-1 were particularly sensitive to decreases in the Na+ gradient induced either by lowering the Na+ concentration in the medium or by treating the tissue with ouabain or by a previous treatment with acetylcholine. Amiloride partially inhibited the response induced by endothelin-1 indicating that Na+ channels and/or Na+/H+ exchange are probably involved in its action. Our results suggest that the contractile response induced by endothelin-1 in the isolated guinea-pig ileum depends greatly on Na+ ions, in contrast to the responses observed in vascular smooth muscle.

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1 The biphasic (relaxation-contraction) response of the isolated duodenum was used to study the reactivity of non-vascular smooth muscles in genetic (SHR) and renal hypertensive rats compared to their respective controls (WKY and Wistar). 2 For the contractile component of the response to bradykinin, the duodenum from WKY rats was more sensitive, whereas the duodenum from SHR was both more sensitive and hyperreactive, compared to that from Wistar rats. 3 The relaxant component of the response to bradykinin was present in the duodenum of both WKY rats and SHR, but was concentration-dependent only in the WKY group. 4 The relaxant response to K+ was very small in SHR, and was not concentration-dependent. 5 The concentration-response curves for relaxant responses to adrenaline and for contractile responses to acetylcholine did not differ in the SHR and WKY groups. 6 Ca2+/Mg2+-ATPase activity was found to be markedly reduced in the SHR group. 7 No qualitative or quantitative differences were observed between the responses of the duodenum of renal hypertensive rats and those of their normotensive controls. 8 It is proposed that the altered reactivity of the SHR duodenum is due to changes in ion handling by the smooth muscle cell membrane.