Superoxide anion impairs contractility in cultured aortic smooth muscle cells.
We examined the effects of superoxide anion (O) generated by xanthine plus xanthine oxidase (X/XO) on the intracellular Ca(2+) concentration ([Ca(2+)](i)) and muscle contractility in cultured bovine aortic smooth muscle cells (BASMC). Cells were grown on collagen-coated dish for the measurement of [Ca(2+)](i). Pretreatment with X/XO inhibited ATP-induced Ca(2+) transient and Ca(2+) release-activated Ca(2+) entry (CRAC) after thapsigargin-induced store depletion, both of which were reversed by superoxide dismutase (SOD). In contrast, Ca(2+) transients induced by high-K(+) solution and Ca(2+) ionophore A-23187 were not affected by X/XO. BASMC-embedded collagen gel lattice, which was pretreated with xanthine alone, showed contraction in response to ATP, thapsigargin, high-K(+) solution, and A-23187. Pretreatment of the gel with X/XO impaired gel contraction not only by ATP and thapsigargin, but also by high-K(+) solution and A-23187. The X/XO-treated gel showed normal contraction; however, when SOD was present during the pretreatment period. These results indicate that O(2)(-) attenuates smooth muscle contraction by impairing CRAC, ATP-induced Ca(2+) transient, and Ca(2+) sensitivity in BASMC.
Kimura
Chiwaka
C
Department of Pharmacology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
Cheng
Wei
W
Hisadome
Kazunari
K
Wang
Yi-Ping
YP
Koyama
Tetsuya
T
Karashima
Yuji
Y
Oike
Masahiro
M
Ito
Yushi
Y
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D002417:Cattle; D002478:Cells, Cultured; D003094:Collagen / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005782:Gels; D007093:Imidazoles; D007424:Intracellular Fluid / Q000378:metabolism; D007476:Ionophores / Q000494:pharmacology; D008163:Luminescent Measurements; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D011188:Potassium / Q000494:pharmacology; D011719:Pyrazines; D013482:Superoxide Dismutase / Q000378:metabolism; D013481:Superoxides / Q000032:analysis / Q000378:metabolism / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology; D019820:Xanthine / Q000378:metabolism; D014969:Xanthine Oxidase / Q000378:metabolism
D004791:Enzyme Inhibitors; D005782:Gels; D007093:Imidazoles; D007476:Ionophores; D011719:Pyrazines; D013481:Superoxides; C063412:2-methyl-6-(4-methoxyphenyl)-3,7-dihydroimidazo(1,2-alpha)pyrazin-3-one; D019820:Xanthine; D000255:Adenosine Triphosphate; D003094:Collagen; D013482:Superoxide Dismutase; D014969:Xanthine Oxidase; D011188:Potassium; D002118:Calcium