Ibudilast-induced decreases in cytosolic Ca(2+) level and contraction in rat aorta.
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 [Ca(2+)](i) level in a concentration-dependent manner, to the same degree. 3-Isobutyl-1-methylxanthine (IBMX) inhibited PE-induced contraction and [Ca(2+)](i) level in a concentration-dependent manner, but it inhibited high K(+)-induced contraction without decrease of [Ca(2+)](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 microM ibudilast inhibited the extracellularly added Ca(2+)-induced muscle tension and increases in [Ca(2+)](i) level during high K(+) depolarization. These results suggested that ibudilast inhibited PE- and high K(+)-induced muscle contractions mainly by the inhibition of [Ca(2+)](i) level in endothelium-denuded rat aorta.
Division of Veterinary Pharmacology, Nippon Veterinary and Life Science University, Musashino, Tokyo, Japan. t-kaneda@nvlu.ac.jp
Takeharu
T
Kaneda
Yasushi
Y
Konno
Norimoto
N
Urakawa
Shinjiro
S
Nakajyo
Kazumasa
K
Shimizu
D015056:1-Methyl-3-isobutylxanthine / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009129:Muscle Tonus / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D010656:Phenylephrine; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D011188:Potassium / Q000378:metabolism; D011725:Pyridines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*; D014700:Verapamil / Q000008:administration & dosage / Q000494:pharmacology; D007212:Indolizines; D011720:Pyrazoles
D015056:1-Methyl-3-isobutylxanthine; D002118:Calcium; D000242:Cyclic AMP; D006152:Cyclic GMP; D010656:Phenylephrine; D010726:Phosphodiesterase Inhibitors; D011188:Potassium; D011725:Pyridines; D014665:Vasodilator Agents; D014700:Verapamil; C038366:ibudilast; D007212:Indolizines; D011720:Pyrazoles