Endothelin-1 inhibits and enhances contraction of porcine coronary arterial strips with an intact endothelium

Using front-surface fluorometry and fura-2-loaded porcine coronary arterial strips with an intact endothelium, changes in cytosolic Ca²⁺ concentrations ([Ca²⁺]i) and tension of smooth muscle were simultaneously monitored in an attempt to determine the vasoactive properties of endothelin-1 (ET-1). ET-1 in low concentrations (0.1-1nM) caused a significant transient decrease in [Ca²⁺]i and tension of the strips precontracted with 10^-7M U-46619. The maximal decreases in [Ca²⁺]i and tension were obtained with 0.6nM ET-1. In higher concentrations (1nM-100nM), there was no reduction in [Ca²⁺]i or tension; the contraction induced by U-46619 was potentiated. The decreases in [Ca²⁺]i and tension induced by ET-1 were inhibited by the mechanical removal of the endothelium or by pretreatment with N^G-nitro-L-arginine and were slightly attenuated by indomethacin. Thus, ET-1 in low concentrations can induce endothelium-dependent transient relaxations accompanied by transient reductions of [Ca²⁺]i in isolated porcine coronary arteries. This effect is mainly mediated by the release of endothelium-derived relaxing factor.