Activated oxygen metabolites as regulators of vascular tone.
Oxygen metabolites have been reported to produce vasoconstriction and/or vasodilation in a variety of in vitro or in vivo vascular preparations. Certain basic mechanisms appear to contribute to these responses. Hydrogen peroxide can produce either vasodilation or constriction via stimulation of prostaglandins. The soluble form of guanylate cyclase in vascular smooth muscle, an enzyme which produces the intracellular mediator of relaxation cyclic GMP, is also a site of action of vasoactive O2 metabolites. Guanylate cyclase is directly activated by nanomolar concentrations of nitric oxide (produced by endothelial cells or nitrovasodilator drugs) or H2O2 (via its metabolism by catalase). These cyclic GMP-mediated mechanisms of relaxation are inhibited by superoxide anion, produced from endogenous sources after inhibition of superoxide dismutase or produced by pharmacological agents that undergo redox cycling. In addition, O2 metabolites may modulate vascular tone via the chemical destruction of physiological contractile agents (e.g. norepinephrine) and relaxant agents (e.g. nitric oxide), and via injury to cells important for the regulation of vascular tone (e.g. endothelium). We have found in a variety of preparations that reexposure to O2 after a brief period of severe hypoxia produces vascular responses that appear to be mediated by intracellular H2O2 generation. Thus, active O2 species may contribute to vascular responses in pathophysiological situations associated with their formation (e.g. inflammation, ischemia/reperfusion, etc.) and to the physiological regulation of vascular tone produced by changes in O2 tension (e.g. reactive hyperemia, hypoxic vasoconstriction, etc).
Wolin
M S
MS
Department of Physiology, New York Medical College, Valhalla.
D000818:Animals; D001783:Blood Flow Velocity / Q000502:physiology*; D004730:Endothelium, Vascular / Q000502:physiology; D005609:Free Radicals; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D009569:Nitric Oxide / Q000502:physiology; D010100:Oxygen / Q000502:physiology*; D014655:Vascular Resistance / Q000502:physiology*
D005609:Free Radicals; D009569:Nitric Oxide; D010100:Oxygen