Differential effects of EPA (eicosapentaenoic acid) on the Ca²⁺-dependent and Ca²⁺-independent contractions of vascular smooth muscles

Abstract

The Ca²⁺-independent contraction of vascular smooth muscles (VSMs) mediated by Rho-kinase plays a central role in the pathogenesis of abnormal contraction of VSMs such as vasospasm. Previously, we identified SPC (sphingosylphosphorylcholine) as a novel signaling molecule which causes Ca²⁺-independent VSM contraction through the activation of Rho-kinase, without the increase in intracellular Ca2+ concentration ([Ca²⁺]_i). Furthermore, we identified EPA (eicosapentaenoic acid) as a specific inhibitor of the Ca²⁺-independent contraction. Here we examined the effects of EPA on the [Ca²⁺]_i and the tension of VSMs, both of which were measured simultaneously by loading VSM strip with fura-2. SPC induced VSM contraction without changing [Ca²⁺]_i, whereas high K⁺-depolarization and U46619 induced VSM contraction with the increase in [Ca²⁺]_i. When the contraction by those stimuli reached the maximum and steady state, EPA was applied. EPA had an inhibitory effect on the contraction induced by SPC and U46619, but did not inhibit the contraction induced by high K⁺-depolarization. Interestingly, EPA had an inhibitory effect on the [Ca²⁺]_i increase induced by U46619, but not on the [Ca²⁺]_i increase induced by high K⁺-depolarization. In this study, we also analyzed the steric effects of EPA on these vascular actions. [Jpn J Physiol 54 Suppl:S120 (2004)]