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Intrarenal superoxide dismutase normalizes renal vascular resistance in rabbits with pacing induced heart failure
Author(s) -
Clayton Sarah C,
Curry Pamela L,
Li Yu,
Zucker Irving H
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.lb710
Subject(s) - renal blood flow , kidney , superoxide dismutase , medicine , oxidative stress , endocrinology , vascular resistance , renal circulation , heart failure , hemodynamics , chemistry
The cardio‐renal syndrome represents a major complication in heart failure (HF) patients, but the underlying mechanisms are not completely understood. The sympathetic nervous system and the renin‐angiotensin II system are likely to induce oxidative stress in the kidney in chronic HF. We hypothesized that in rabbits with HF reducing oxidant stress with superoxide dismutase (SOD) would improve renal blood flow in HF. In rabbits with HF (verified by echocardiography), renal blood flow was reduced (37.6 ± 1.7 ml/min in sham, vs. 29.2 ± 1.7 ml/min in HF, P=0.001). Unilateral intrarenal infusion of CuZn‐superoxide dismutase conjugated to polyethylene glycol (PEG‐SOD) at a dose of 0.30 U/kg/hr for 7 days tended to increase renal blood flow in HF rabbits (35.9 ± 2.1 ml/min). Renal vascular resistance was increased from sham (1.96 ± 0.10 mm Hg/ml/min, sham, vs. 2.36 ± 0.16 mm Hg/ml/min, HF, P=0.03) which was prevented by PEG‐SOD infusion (1.45 ± 0.14 mm Hg/ml/min, P=0.03 vs. HF alone). We confirmed that PEG‐SOD treatment reduced dihydroethidium staining in the treated kidneys from HF rabbits but not the contralateral, untreated kidneys, suggesting the beneficial effect was limited to the treated kidney and not from a systemic effect. These results suggest the change in renal hemodynamics in HF is due to intrarenal oxidative stress and could implicate a potential therapeutic strategy to improve the cardio‐renal syndrome.