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

Endothelins (ETs) contract de-endothelialized rings from left descending co ronary artery via ETA or ETB receptors. Here we test the hypothesis that th e actions of ETA and ETB receptors are similar in their sensitivities to da mage by hydrogen peroxide. In Ca2+-containing Krebs' solution, 100 nM of th e ETB agonist IRL1620 produced contractions with significantly smaller forc e (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 peroxi de 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 i n Ca2+, 1.4 +/- 0.1 mM in Ca2+-free) than using IRL1620 (0.32 +/- 0.08 in C a2+, 0.25 +/- 0.01 mM in Ca2+-free). Pretreating microsomes isolated from t he artery smooth muscle with up to 10 mM peroxide did not significantly aff ect I-125-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).