Characterization of the contractile and relaxant action of the endothelin-1 precursor, big endothelin-1, in the isolated rat basilar artery

The presence of functional endothelin converting enzyme (ECE) activity in b asilar artery ring segments was investigated by measuring the contractile a nd relaxant effects of big endothelin (ET)-1. Under resting tension conditi ons cumulative application of big ETI-1 elicited a concentration-related co ntraction with the concentration-effect curve (CEC) shifted to the right ag ainst ET-1 by a factor of 31 and 29 in segments with the endothelium intact or mechanically removed, respectively. Preincubation with the ET(A) recept or antagonist, BQ123, induced an apparently parallel rightwards shift witho ut affecting the maximum contraction. This shift was more pronounced for ET -1 than for big ET-1. With the putative ECE inhibitor phosphoramidon (10(-3 ) M) in the bath a small rightwards shift of the CEC for big ET-1 was obser ved in control segments and a more marked one in de-endothelialized segment s. In segments precontracted with prostaglandin (PG) F-2 alpha big ET-1 ind uced a significant although transient relaxation whereas ET-1 did not. Howe ver, in the presence of BQ123 both ET-1 and big ET-1 elicited concentration -related relaxation with a significantly higher maximum effect obtained wit h big ET-1. The potency was 13 fold higher for ET-1, which is markedly less than that found for contraction. The results, therefore, suggest 1) the pr esence of functional ECE-activity in the rat basilar artery wall, and 2) di fferences in the functional ECE activity located in the endothelium and med ia. (C) 2000 Elsevier Science Inc. All rights reserved.