Ibudilast-Induced Decreases in Cytosolic Ca²⁺ Level and Contraction in Rat Aorta

Abstract

The mechanism by which ibudilast induces vasodilation was examined in isolated endothelium-denuded rat aorta. Ibudilast inhibited the contractions induced by phenylephrine (PE) and high K⁺ with decrease of [Ca²⁺]_i level in a concentration-dependent manner, to the same degree. 3-Isobutyl-1-methylxanthine (IBMX) inhibited PE-induced contraction and [Ca²⁺]_i level in a concentration-dependent manner, but it inhibited high K⁺-induced contraction without decrease of [Ca²⁺]_i level. In comparison with IBMX, the increases of cAMP and cGMP contents in ibudilast were much smaller than that of muscle tension. Ibudilast did not inhibit 12-deoxyphorbol 13-isobutyrate (DPB)-induced contraction in the presence of verapamil. Treatment with 30 μM ibudilast inhibited the extracellularly added Ca²⁺-induced muscle tension and increases in [Ca²⁺]_i level during high K⁺ depolarization. These results suggested that ibudilast inhibited PE- and high K⁺-induced muscle contractions mainly by the inhibition of [Ca²⁺]_i level in endothelium-denuded rat aorta.