Nitric oxide and blood pressure in mice lacking extracellular-superoxide dismutase.
Nitric oxide is a major vasorelaxant and regulator of the blood pressure. The blood vessels contain several active sources of the superoxide radical, which reacts avidly with nitric oxide to form noxious peroxynitrite. There are large amounts of extracellular-superoxide dismutase (EC-SOD) in the vascular wall. To evaluate the importance of EC-SOD for the physiology of nitric oxide, here we studied the blood pressure in mice lacking the enzyme. In chronically instrumented non-anaesthetized mice there was no difference in mean arterial blood pressure between wild-type controls and EC-SOD mutants. Extensive inhibition of nitric oxide synthases with N-monomethyl-L-arginine however resulted in a larger increase in blood pressure, and infusion of the nitric oxide donor nitrosoglutathione caused less reduction in blood pressure in the EC-SOD null mice. We interpret the alterations to be caused by a moderately increased consumption of nitric oxide by the superoxide radical in the EC-SOD null mice. One role of EC-SOD may be to preserve nitric oxide, a function that should be particularly important in vascular pathologies, in which large increases in superoxide formation have been documented.
Department of Medical Biosciences, Clinical Chemistry, Umeå University, SE-901 85, Umeå, Sweden.
Lena M
LM
Jonsson
Daryl D
DD
Rees
Thomas
T
Edlund
Stefan L
SL
Marklund
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D001795:Blood Pressure Determination; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D013482:Superoxide Dismutase / Q000172:deficiency / Q000502:physiology*; D019323:omega-N-Methylarginine / Q000494:pharmacology
D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse; D013482:Superoxide Dismutase