Peroxide sensitivity of endothelin responses in coronary artery smooth muscle: ETA vs. ETB pathways

Endothelins (ETs) contract de-endothelialized rings from left descending coronary artery via ETA or ETB receptors. Here we test the hypothesis that the actions of ETA and ETB receptors are similar in their sensitivities to damage by hydrogen peroxide. In Ca2+-containing Krebs' solution, 100 nM of the ETB agonist IRL1620 produced contractions with significantly smaller force (17.6 ± 1.7 mN) than 50 nM of the ETA + ETB agonist ET-1 (73.2 ± 4.6 mN) (p < 0.05). In Ca2+-free solutions, the contractions due to both agents were significantly smaller (p < 0.05). Pretreating the tissues with peroxide inhibited the contractions produced by either agent. The IC50 values for peroxide were significantly higher (p < 0.05) using ET-1 (1.0 ± 0.3 mM in Ca2+, 1.4 ± 0.1 mM in Ca2+-free) than using IRL1620 (0.32 ± 0.08 in Ca2+, 0.25 ± 0.01 mM in Ca2+-free). Pretreating microsomes isolated from the artery smooth muscle with up to 10 mM peroxide did not significantly affect 125I-ET-1 binding to ETA or ETB receptors (p > 0.05). In comparing the peroxide induced inactivation of the various processes in this artery and based on literature, we conclude that the actions of ETA may also involve a peroxide resistant Ca2+-independent pathway(s).