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ARS Home » Plains Area » Grand Forks, North Dakota » Grand Forks Human Nutrition Research Center » Healthy Body Weight Research » Research » Publications at this Location » Publication #71264
Title: VASCULAR SUPEROXIDE DISMUTASE DEFICIENCY IMPAIRS ENDOTHELIAL VASODILATOR FUNCTION BY TWO DISTINCT MECHANISMS

Author
item LYNCH, SEAN - BOSTON UNIT
item MORROW, JASON - VANDERBILT UNIV
item Klevay, Leslie
item FREI, BALZ - BOSTON UNIV
item VITA, JOSEPH - BOSTON UNIV
item KEANEY, JOHN - BOSTON UNIV

Submitted to: Circulation
Publication Type: Abstract Only
Publication Acceptance Date: 5/16/1996
Publication Date: N/A
Citation: N/A

Interpretive Summary:

Technical Abstract: Normal vascular homeostasis is regulated, in part, by endothelial production of nitric oxide (NO). The action of NO is limited by the local production of superoxide and the activity of SOD. Acute inhibition of SOD results in accelerated inactivation of NO, however, the effects of chronic SOD inhibition are not known. We studied the effect of chronic SOD inhibition using a copper-deficient rat model. Compared to copper-sufficient control rats, endothelium-dependent relaxation in the thoracic aortae of copper-deficient animals was 6-fold calcium lonophore (both P<0.005). There was also a 2-fold reduction in the sensitivity of copper-deficient rat aorta to relaxation with authentic NO (P<0.05). Copper deficiency resulted in a 68% reduction in tissue copper-zinc SOD activity and, a 58% increase in net vascular superoxide production that correlated closely with the magnitude of impairment in acetylcholine- and calcium lonophore-mediated arterial relaxation (R=-0.76 and R=-0.61, respectively; both P<0.05). In contrast, relaxation in response to authentic NO did not correlate well with vascular superoxide (R=0.39; P<0.19). Copper deficiency also resulted in a 2.5-fold increase in plasma esterified F2-isoprostanes, an index of in vivo lipid peroxidation, that was inversely associated with arterial relaxation in response to acetylcholine (R=-0.82; P<0.0009), but not A23187 or authentic NO. Thus, relaxation to both exogenous and endothelium-derived NO. In addition, excess superoxide produces increases in vivo lipid peroxidation that is associated with impaired receptor-mediated endothelium-dependent arterial relaxation.