Redox modulation of vascular tone: focus of potassium channel mechanisms of dilation.
Opening of potassium channels on vascular smooth muscle cells with resultant hyperpolarization plays a central role in several mechanisms of vasodilation. For example, in the arteriolar circulation where tissue perfusion is regulated, there is an endothelial derived hyperpolarizing factor that opens vascular smooth muscle calcium-activated potassium channels, eliciting dilation. Metabolic vasodilation involves the opening of sarcolemmal ATP-sensitive potassium channels. Adrenergic dilation as well as basal vasomotor tone in several vascular beds depend upon voltage-dependent potassium channels in smooth muscle. Thus hyperpolarization through potassium channel opening is a fundamental mechanism for vasodilation. Disease states such as coronary atherosclerosis and its risk factors are associated with elevated levels of reactive oxygen (ROS) and nitrogen species that have well-defined inhibitory effects on nitric oxide-mediated vasodilation. Effects of ROS on hyperpolarization mechanisms of dilation involving opening of potassium channels are less well understood but are very important because hyperpolarization-mediated dilation often compensates for loss of other dilator mechanisms. We review the effect of ROS on potassium channel function in the vasculature. Depending on the oxidative species, ROS can activate, inhibit, or leave unaltered potassium channel function in blood vessels. Therefore, discerning the activity of enzymes regulating production or degradation of ROS is important when assessing tissue perfusion in health and disease.
Gutterman
David D
DD
Cardiovascular Center, Department of Medicine, General Clinical Research Center, VA Medical Center, Medical College of Wisconsin, Milwaukee 53226, USA. dgutt@mcw.edu
Miura
Hiroto
H
Liu
Yanping
Y
D000818:Animals; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D010084:Oxidation-Reduction; D015221:Potassium Channels / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014664:Vasodilation / Q000502:physiology*
D015221:Potassium Channels; D017382:Reactive Oxygen Species