VEGF-121 preserves renal microvessel structure and ameliorates secondary renal disease following acute kidney injury.
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.
Leonard
Ellen C
EC
Dept. of Cellular and Integrative Physiology, Indiana Univ. School of Medicine, 635 Barnhill Dr. MS 334, Indianapolis, IN 46202, USA.
Friedrich
Jessica L
JL
Basile
David P
DP
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*
D017673:Sodium Chloride, Dietary; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D003404:Creatinine
Am J Physiol Renal Physiol. 2002 Jun;282(6):F1150-5
11997332
Am J Physiol. 1989 Dec;257(6 Pt 2):F913-24
2690642
Kidney Int. 2000 Dec;58(6):2390-9
11115072
Ren Fail. 1999 May-Jul;21(3-4):427-31
10416223
Kidney Int. 2007 Jul;72(2):151-6
17495858
Nat Med. 2004 Apr;10(4):363-4
14991049
Am J Physiol Renal Physiol. 2007 Jul;293(1):F269-78
17507599
J Am Soc Nephrol. 2001 Jul;12(7):1448-1457
11423573
Am J Physiol Renal Physiol. 2005 Mar;288(3):F568-77
15536165
Am J Physiol Renal Physiol. 2001 Nov;281(5):F887-99
11592947
Kidney Int. 2001 Oct;60(4):1297-308
11576344
J Am Soc Nephrol. 2006 Jun;17(6):1503-20
16707563
Am J Physiol Renal Physiol. 2003 Feb;284(2):F338-48
12388385
Hypertension. 1996 Mar;27(3 Pt 2):688-92
8613226
J Pharmacol Exp Ther. 2003 Mar;304(3):905-12
12604664
J Am Soc Nephrol. 2002 Mar;13(3):806-816
11856789
Kidney Int. 1997 Nov;52(5):1169-79
9350640
Am J Physiol Renal Physiol. 2008 Apr;294(4):F928-36
18272597
Am J Physiol Renal Physiol. 2003 Aug;285(2):F191-8
12684225
Am J Physiol Renal Physiol. 2006 Dec;291(6):F1248-54
16804104
Hypertension. 1999 Jul;34(1):151-9
10406839
Curr Opin Nephrol Hypertens. 1998 Jul;7(4):419-24
9690042
Kidney Int. 2002 Nov;62(5):1539-49
12371954
Am J Physiol Renal Physiol. 2004 May;286(5):F893-902
15075185
Curr Opin Nephrol Hypertens. 2004 Jan;13(1):1-7
15090853
Am J Physiol Renal Physiol. 2001 Apr;280(4):F727-36
11249864
Kidney Int. 1997 Jul;52(1):182-94
9211361
Am J Physiol Regul Integr Comp Physiol. 2008 Apr;294(4):R1234-9
18256138
Hypertension. 1999 Apr;33(4):1013-9
10205240
Kidney Int. 1997 Dec;52(6):1570-8
9407502
Cell Struct Funct. 2001 Feb;26(1):25-35
11345501
Am J Physiol. 1999 Nov;277(5):H1985-96
10564155