Opposing effects of oxidants and antioxidants on K+ channel activity and tone in rat vascular tissue.
K+ channels regulate tone in both the systemic and pulmonary circulations. K+ channel inhibition leads to membrane depolarization, Ca2+ influx and vasoconstriction; K+ channel activation leads to hyperpolarization and vasodilatation. The sulfhydryl oxidant diamide opens K+ channels in pulmonary smooth muscle and acts as a potent vasodilator in perfused lungs. We examined the hypothesis that antioxidants cause constriction and oxidants cause relaxation through their effects on K+ channels in vascular smooth muscle. The oxidant diamide (380 microM and 3.8 mM) inhibited the reduction of cytochrome C by ferrous sulphate in vitro whilst the antioxidants co-enzyme Q10 (770 microM) and duroquinone (700 microM) increased the rate of reduction. Both antioxidants caused dose-dependent constriction of endothelium-intact and -denuded rat pulmonary artery and aortic rings. This constriction could be reversed by 1 microM diamide. Co-enzyme Q10 and duroquinone (both at 100 microM) partially inhibited (approximately 30%) whole-cell K+ channel currents and depolarized membranes of isolated pulmonary artery smooth muscle cell recorded using the amphotericin-perforated-patch-clamp technique. Diamide (100 microM) increased whole-cell K+ channel currents and hyperpolarized the membrane. The data suggest that oxidants and antioxidants may modulate vascular tone via an effect on K+ channels.
Minneapolis Veteran's Affairs Medical Centre, MN, USA.
H L
HL
Reeve
E K
EK
Weir
D P
DP
Nelson
D A
DA
Peterson
S L
SL
Archer
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D016227:Benzoquinones / Q000494:pharmacology; D003574:Cytochrome c Group / Q000378:metabolism; D003958:Diamide / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000502:physiology; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects; D009129:Muscle Tonus / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D016877:Oxidants / Q000494:pharmacology*; D010084:Oxidation-Reduction; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D014451:Ubiquinone / Q000494:pharmacology
D000975:Antioxidants; D016227:Benzoquinones; D003574:Cytochrome c Group; D016877:Oxidants; D015221:Potassium Channels; D003958:Diamide; D014451:Ubiquinone; C034257:duroquinone