Inactivation of extracellular superoxide dismutase contributes to the development of high-volume hypertension.
OBJECTIVE
Extracellular superoxide dismutase (ecSOD) lowers superoxide anions and maintains vascular nitric oxide level. We studied the function of ecSOD in high-volume hypertension induced by the 1-kidney-1-clip model in wild-type, ecSOD-/- mice, and endothelial nitric oxide synthase (eNOS)-/- mice.


RESULTS
The 1-kidney-1-clip model resulted in impaired endothelium-dependent relaxation and hypertension and vascular oxidative stress in wild-type and ecSOD-/- mice. Recombinant ecSOD lowered the blood pressure and improved aortic nitric oxide bioavailability in wild-type and ecSOD-/- but not eNOS-/- mice. ecSOD had no effect on blood pressure in eNOS-/- or wild-type mice treated with a nitric oxide synthase inhibitor. The 1-kidney-1-clip model markedly induced ecSOD protein expression, whereas activity was increased by only 25%, suggesting a partial inactivation of ecSOD in high-volume hypertension. Incubation of aortic segments with peroxynitrite or hydrogen peroxide attenuated ecSOD activity, but peroxynitrite did not induce tyrosine nitration of ecSOD, suggesting oxidative inactivation of the enzyme. Administration of polyethyleneglycol-catalase for 3 days selectively lowered the blood pressure in ecSOD+/+ but not ecSOD-/- mice and improved nitric oxide bioavailability. In contrast, acute application of catalase had no effect.


CONCLUSIONS
Nitric oxide mediates the vascular effects of ecSOD. Vascular dysfunction in 1-kidney-1-clip model hypertension is partially a consequence of inactivation of ecSOD by reactive oxygen species.
Jung
Oliver
O
Institut für Kardiovaskuläre Physiologie, Klinikum der J.W. Goethe-Universität, Theodor-Stern-Kai 7, D-60596 Frankfurt am Main, Germany.
Marklund
Stefan L
SL
Xia
Ning
N
Busse
Rudi
R
Brandes
Ralf P
RP
D000818:Animals; D001795:Blood Pressure Determination; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D005109:Extracellular Matrix; D006973:Hypertension / Q000175:diagnosis / Q000201:enzymology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009392:Nephrectomy; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D018384:Oxidative Stress; D011336:Probability; D012680:Sensitivity and Specificity; D013482:Superoxide Dismutase / Q000378:metabolism*
D052250:Nitric Oxide Synthase Type III; D013482:Superoxide Dismutase