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Arginase inhibition does not improve aortic endothelial‐dependent relaxation in rats with chronic kidney disease
Author(s) -
Martens Christopher R,
Schellhardt Taylor,
LenEdwards Shan L,
Edwards David G
Publication year - 2011
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.25.1_supplement.641.16
Arginase (Arg) impairs endothelial‐dependent relaxation (EDR) in aging and hypertension. The PURPOSE of this study was to determine if Arg inhibition or L‐arginine (L‐arg) treatment improves EDR in chronic kidney disease (CKD). METHODS 10 rats (Sprague‐Dawley; 12 wk old) underwent either 5/6 ablation/infarction (CKD) or SHAM surgery. After 8 weeks, EDR was assessed in aortic rings (acetylcholine; 10 −9 − 10 −5 M) pretreated (30 min) in one of four conditions: control (CON), Arg inhibition (BEC), L‐arg, BEC+L‐arg. Changes in LogEC 50 and maximal effect (E max ) were analyzed by unpaired t‐tests. Arg content was analyzed by western blot (WB). RESULTS LogEC50 was shifted and E max significantly attenuated in CON rings between CKD and SHAM (LogEC50: CKD=−6.53 ± 0.116, SHAM=−7.71 ± 0.110, p<0.0001; Emax: CKD: 39.5 ± 4.75, SHAM=3.11 ± 4.34, p<0.01). L‐Arg and BEC treatments alone or in combination were ineffective at restoring EDR in CKD rings. WB analysis showed no significant difference in aortic Arg1 (p=0.203) or Arg2 (p=0.319) content (normalized to μ‐actin) between groups. CONCLUSION Arg inhibition and/or L‐arg does not restore EDR in CKD. Further study is needed to elucidate the mechanisms of impaired EDR in CKD. Supported by: P20 RR016472