Journal Article

Endothelin contraction in pig coronary: Receptor types and Ca2+-mobilization

Grover, A.K., Elmoselhi, A.B.

1997

Overview

Endothelin is one of the most potent vasoconstrictors known. It plays an important role in the regulation of vascular tone and in the development of many cardiovascular diseases. This study focuses on the receptor types and the Ca^sup 2+^ mobilization responsible for endothelin-1 (ET-1) contraction in de-endothelialized pig coronary artery rings. ET-1 contracted the artery rings with an EC^sub 50^ = 6.5 ± 1 nM and a maximum contraction which was 98.6 ± 9% of the contraction produced by 60 mM KCl. BQ123 (5 µM), an ET^sub A^ antagonist, reversed 78 ± 3% of the ET-1 contraction (50 nM). IRL1620, a selective ET^sub B^ agonist, produced 23 ± 3% of the total ET-1 contraction with an EC^sub 50^ = 12.7 ± 2 nM. More than 85% of the contraction due to 100 nM IRL 1620 was inhibited by 200 nMBQ788, an ET^sub B^ antagonist. Therefore, approximately 80% of the ET-1 contraction in this artery occurred via ET^sub A^ receptors, and the other 20% was mediated by ET^sub B^ receptors. To assess the Ca^sup 2+^ pools utilized during the ET-1 response, ET-1 contraction was also examined in medium containing an L-type Ca^sup 2+^ channel blocker nitrendipine, and in Ca^sup 2+^ free medium containing 0.2 mM EGTA. In Ca^sup 2+^ containing medium the contraction elicited by ET-1 was 98.6 ± 9% of the KCl contraction, however, in the presence 10 µM nitrendipine the ET-1 induced contraction was 54 ± 7% of the KCl contraction, and in Ca^sup 2+^-free medium it was 13 ± 2%. Similarly, the IRL 1620 contractions in Ca^sup 2+^ containing medium, in the presence of nitrendipine and in Ca^sup 2+^-free medium were 22.4 ± 3%, 12 ± 3% and 11 ± 2% of the KCl response respectively. Thus, both ET^sub A^ and ET^sub B^ contractions utilize extracellular Ca^sup 2+^ pools via L-type Ca^sup 2+^ channels and other undefined route(s), as well as intracellular Ca^sup 2+^ pools. In the pig coronary artery smooth muscle, ET-1 contractions occur predominantly via ET^sub A^ receptors, with ET^sub B^ receptors using similar Ca^sup 2+^ mobilization pathways, but the ET^sub B^ receptors appear to use the intracellular Ca^sup 2+^ stores to a greater extent.[PUBLICATION ABSTRACT]

• Publisher: Springer Nature B.V
• Subject: Cardiovascular diseases / Muscular system / Swine / Veins & arteries