Sun Endothelin‐1 regulates cardiac L‐type calcium channels via NAD(P)H oxidase‐derived superoxide

It has been shown that reactive oxygen species (ROS) are involved in the intracellular signaling response to G-protein coupled recep-tor stimuli in vascular smooth muscle cells and in neurons. In the present study, we tested the hypothesis that NAD(P)H oxidase-derived ROS are involved endothelin-1 (ET-1)-induced L-type cal-cium channel activation in isolated cardiac myocytes. ET-1 (10 nM) induced a 2-fold increase in L-type calcium channel open-state probability (NPo). This effect of ET-1 was abolished by the ETA receptor antagonist cyclo(D-Trp-D-Asp-Pro-D-Val-Leu) [BQ-123 (1 M)] but was not altered in the presence of an ETB receptor antagonist N-cis-2,6-dimethylpiperidinocarbonyl-b-tBu-Ala-D-Trp(1-methoxycarbonyl)-D-Nle-OH [BQ-788 (1 M)]. Pre-treatment of cells with the ROS scavenger tempol (100 M), polyethylene glycol-superoxide dismutase (SOD, 25 U/ml), or th