Enzymatic pathways involved in the generation of endothelin-1(1-31) from exogenous big endothelin-1 in the rabbit aorta.

British Journal of Pharmacology
Carlos R TirapelliPedro D'Orleans-Juste

Abstract

We investigated whether blood vessels contribute to the production of ET-1(1-31) from exogenous big endothelin-1 (BigET-1) in the rabbit and assessed which enzymes are involved in this process. Vascular reactivity experiments, using standard muscle bath procedures, showed that BigET-1 induces contraction in endothelium-intact rabbit aortic rings. Preincubation of the rings with phosphoramidon, CGS35066 or thiorphan reduced BigET-1-induced contraction. Conversely, chymostatin did not affect BigET-1-induced contraction. Thiorphan and phosphoramidon, but not CGS35066 or chymostatin, reduced ET-1(1-31)-induced contraction. None of the enzymatic inhibitors affected the contraction afforded by ET-1.BQ123-, but not BQ788-, selective antagonists for ET(A) and ET(B) receptors, respectively, produced concentration-dependent rightward displacements of the ET-1(1-31) and ET-1 concentration-response curves. By the use of enzymatic assays, we found that the aorta, as well as the heart, lung, kidney and liver, possess a chymase-like activity. Enzyme immunoassays detected significant levels of Ir-ET-1(1-31) in bathing medium of aortas after the addition of BigET-1 (30 nM). Neither thiorphan nor chymostatin altered the levels of Ir-ET-1(1-31). ...Continue Reading

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Citations

Jun 3, 2008·Canadian Journal of Physiology and Pharmacology·W GoettschH Morawietz
Dec 1, 2007·Clinical and Experimental Pharmacology & Physiology·Karigowda J Dammanahalli, Zhongjie Sun
May 11, 2007·Expert Review of Cardiovascular Therapy·Glaucia CalleraRhian M Touyz
Mar 4, 2011·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Stephane L BourqueMichael A Adams
Aug 17, 2021·Frontiers in Physiology·Mazhar PashaChristy-Lynn M Cooke
Aug 5, 2008·Vascular Pharmacology·P D'Orléans-JusteE Simard
Jul 6, 2010·Peptides·Ricardo Fernández-MusolesJuan B Salom

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