The Effects of Endothelin-1 On the Responses of Arteries and Veins To Bay-k-8644 - Influence of the Endothelium and Sin-1

(1991) SATELLITE SYMP OF THE INTERNATIONAL UNION OF PHARMACOLOGY : EDRF AND EDRF RELATED SUBSTANCES — Location: ANTWERP(Belgium) (28.June.1990)

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Abstract
We investigated the effects of threshold doses of endothelin-1 (ET-1) on contractions of rabbit jugular vein evoked by the calcium agonist Bay K 8644, either in intact or in endothelium-denuded preparations, and we compared the results with those obtained previously in rat aorta. Relaxation of K+ contraction by acetylcholine 1-mu-M was used to test the presence of functional endothelial cells: thereafter the preparations were preincubated during 1 h in the presence or in the absence of ET-1 10 pM before being exposed to cumulative doses of Bay K 8644 ranging from 3 to 300 nM. Cumulative concentrations of Bay K 8644 evoked contractions in about 80% of control rabbit jugular veins, with or without endothelium. In the presence of ET-1 10 pM, the percentage of contractile responses was significantly decreased in intact rings and was significantly increased in endothelium denuded rings. The inhibition exerted by ET-1 10 pM on Bay K 8644 contractile effect in preparations with intact endothelium was reversed to potentiation by methylene blue (3-mu-M) and by nitroarginine (20-mu-M for 30 min). We conclude that threshold concentrations of ET-1 increase the direct action of Bay K 8644 in smooth muscle cells of rabbit jugular vein indicating an increase of the gating of voltage-operated calcium channels. Moreover, in rabbit jugular vein with intact endothelium, those threshold concentrations of ET-1 evoke EDRF release which decreases the responsiveness of the vein to Bay K 8644.
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Salomone, S., & Godfraind, T. (1991). The Effects of Endothelin-1 On the Responses of Arteries and Veins To Bay-k-8644 - Influence of the Endothelium and Sin-1. Journal of Cardiovascular Pharmacology, 17(Suppl 3), S152-S158. https://doi.org/10.1097/00005344-199117003-00029 (Original work published 1991)