Enhanced peroxynitrite formation is associated with vascular aging
B Van Der Loo, R Labugger, JN Skepper… - The Journal of …, 2000 - rupress.org
B Van Der Loo, R Labugger, JN Skepper, M Bachschmid, J Kilo, JM Powell…
The Journal of experimental medicine, 2000•rupress.orgVascular aging is mainly characterized by endothelial dysfunction. We found decreased free
nitric oxide (NO) levels in aged rat aortas, in conjunction with a sevenfold higher expression
and activity of endothelial NO synthase (eNOS). This is shown to be a consequence of age-
associated enhanced superoxide (· O2−) production with concomitant quenching of NO by
the formation of peroxynitrite leading to nitrotyrosilation of mitochondrial manganese
superoxide dismutase (MnSOD), a molecular footprint of increased peroxynitrite levels …
nitric oxide (NO) levels in aged rat aortas, in conjunction with a sevenfold higher expression
and activity of endothelial NO synthase (eNOS). This is shown to be a consequence of age-
associated enhanced superoxide (· O2−) production with concomitant quenching of NO by
the formation of peroxynitrite leading to nitrotyrosilation of mitochondrial manganese
superoxide dismutase (MnSOD), a molecular footprint of increased peroxynitrite levels …
Vascular aging is mainly characterized by endothelial dysfunction. We found decreased free nitric oxide (NO) levels in aged rat aortas, in conjunction with a sevenfold higher expression and activity of endothelial NO synthase (eNOS). This is shown to be a consequence of age-associated enhanced superoxide (·O2−) production with concomitant quenching of NO by the formation of peroxynitrite leading to nitrotyrosilation of mitochondrial manganese superoxide dismutase (MnSOD), a molecular footprint of increased peroxynitrite levels, which also increased with age. Thus, vascular aging appears to be initiated by augmented ·O2− release, trapping of vasorelaxant NO, and subsequent peroxynitrite formation, followed by the nitration and inhibition of MnSOD. Increased eNOS expression and activity is a compensatory, but eventually futile, mechanism to counter regulate the loss of NO. The ultrastructural distribution of 3-nitrotyrosyl suggests that mitochondrial dysfunction plays a major role in the vascular aging process.
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