title: VEGF-121 preserves renal microvessel structure and ameliorates secondary renal disease following acute kidney injury.
abstract: Acute kidney injury induced by renal ischemia-reperfusion (I/R) compromises microvascular density and predisposes to chronic kidney disease (CKD) and sodium-dependent hypertension. VEGF-121 was administered to rats fed a standard (0.4%) sodium diet at various times following recovery from I/R injury for up to 35 days. VEGF-121 had no effect on the initial loss of renal function, as indicated by serum creatinine levels measured 24 h after injury. Serum creatinine levels declined thereafter, indicative of renal repair. Rats were then switched to an elevated (4.0%) sodium diet for an additional 28 days to induce CKD. The 4.0% sodium diet enhanced renal hypertrophy, interstitial volume, albuminuria, and cardiac hypertrophy relative to postischemic animals maintained on the 0.4% sodium diet. Administration of VEGF-121 from day 0 to 14, day 0 to 35, or day 3 to 35 after I/R suppressed the effects of sodium diet on CKD development, while delayed administration of VEGF-121 from day 21 to 35 had no effect. Endothelial nitric oxide synthase protein levels were upregulated in postischemic animals, and this effect was significantly increased by the 4.0% sodium diet but was not influenced by prior treatment with VEGF. Conversely, microvascular density was preserved in postischemic animals treated with VEGF-121 relative to vehicle-treated postischemic animals. These data suggest that early, but not delayed, treatment with VEGF-121 can preserve vascular structure after ischemia and influence chronic renal function in response to elevated sodium intake.
authors.affiliation: Dept. of Cellular and Integrative Physiology, Indiana Univ. School of Medicine, 635 Barnhill Dr. MS 334, Indianapolis, IN 46202, USA.
authors.forename: Ellen C
authors.initials: EC
authors.lastname: Leonard
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Friedrich
authors.forename: David P
authors.initials: DP
authors.lastname: Basile
mesh_terms: D058186:Acute Kidney Injury / Q000473:pathology / Q000503:physiopathology* / Q000517:prevention & control*; D000818:Animals; D003404:Creatinine / Q000097:blood; D007668:Kidney / Q000293:injuries*; D007677:Kidney Function Tests; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology*; D017673:Sodium Chloride, Dietary / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000627:therapeutic use*
chemical_list: D017673:Sodium Chloride, Dietary; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D003404:Creatinine
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