diamide and duroquinone

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.

Topics: Animals; Antioxidants; Aorta, Thoracic; Benzoquinones; Cytochrome c Group; Diamide; Endothelium, Vascular; In Vitro Techniques; Membrane Potentials; Muscle Contraction; Muscle Tonus; Muscle, Smooth, Vascular; Oxidants; Oxidation-Reduction; Patch-Clamp Techniques; Potassium Channels; Rats; Ubiquinone