PMID- 18459944
OWN - NLM
STAT- MEDLINE
DCOM- 20090220
LR  - 20220311
IS  - 1470-8736 (Electronic)
IS  - 0143-5221 (Print)
IS  - 0143-5221 (Linking)
VI  - 116
IP  - 1
DP  - 2009 Jan
TI  - Administration of a substituted adamantyl urea inhibitor of soluble epoxide 
      hydrolase protects the kidney from damage in hypertensive Goto-Kakizaki rats.
PG  - 61-70
LID - 10.1042/CS20080039 [doi]
AB  - Hypertension and Type 2 diabetes are co-morbid diseases that lead to the 
      development of nephropathy. sEH (soluble epoxide hydrolase) inhibitors are 
      reported to provide protection from renal injury. We hypothesized that the sEH 
      inhibitor AUDA [12-(3-adamantan-1-yl-ureido)-dodecanoic acid] protects the kidney 
      from the development of nephropathy associated with hypertension and Type 2 
      diabetes. Hypertension was induced in spontaneously diabetic GK (Goto-Kakizaki) 
      rats using AngII (angiotensin II) and a high-salt diet. Hypertensive GK rats were 
      treated for 2 weeks with either AUDA or its vehicle added to drinking water. MAP 
      (mean arterial pressure) increased from 118+/-2 mmHg to 182+/-20 and 187+/-6 mmHg 
      for vehicle and AUDA-treated hypertensive GK rats respectively. AUDA treatment 
      did not alter blood glucose. Hypertension in GK rats resulted in a 17-fold 
      increase in urinary albumin excretion, which was decreased with AUDA treatment. 
      Renal histological evaluation determined that AUDA treatment decreased glomerular 
      and tubular damage. In addition, AUDA treatment attenuated macrophage 
      infiltration and inhibited urinary excretion of MCP-1 (monocyte chemoattractant 
      protein-1) and kidney cortex MCP-1 gene expression. Taken together, these results 
      provide evidence that sEH inhibition with AUDA attenuates the progression of 
      renal damage associated with hypertension and Type 2 diabetes.
FAU - Olearczyk, Jeffrey J
AU  - Olearczyk JJ
AD  - Vascular Biology Center, Medical College of Georgia, Augusta, GA 30912, USA.
FAU - Quigley, Jeffrey E
AU  - Quigley JE
FAU - Mitchell, Bradford C
AU  - Mitchell BC
FAU - Yamamoto, Tatsuo
AU  - Yamamoto T
FAU - Kim, In-Hae
AU  - Kim IH
FAU - Newman, John W
AU  - Newman JW
FAU - Luria, Ayala
AU  - Luria A
FAU - Hammock, Bruce D
AU  - Hammock BD
FAU - Imig, John D
AU  - Imig JD
LA  - eng
GR  - P01 DK038226-210011/DK/NIDDK NIH HHS/United States
GR  - R01 HL059699/HL/NHLBI NIH HHS/United States
GR  - P01 HL074167/HL/NHLBI NIH HHS/United States
GR  - P01 DK038226/DK/NIDDK NIH HHS/United States
GR  - R01 HL059699-09/HL/NHLBI NIH HHS/United States
GR  - HL-59699/HL/NHLBI NIH HHS/United States
GR  - HL-74167/HL/NHLBI NIH HHS/United States
GR  - P01 HL074167-05/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Clin Sci (Lond)
JT  - Clinical science (London, England : 1979)
JID - 7905731
RN  - 0 (12-(3-adamantan-1-ylureido)dodecanoic acid)
RN  - 0 (Antihypertensive Agents)
RN  - 0 (Blood Glucose)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Insulin)
RN  - 0 (Lauric Acids)
RN  - 0 (Lipids)
RN  - 0 (NF-kappa B)
RN  - EC 3.3.2.- (Epoxide Hydrolases)
RN  - PJY633525U (Adamantane)
SB  - IM
MH  - Adamantane/*analogs & derivatives/therapeutic use/urine
MH  - Animals
MH  - Antihypertensive Agents/*therapeutic use
MH  - Blood Glucose/metabolism
MH  - Diabetes Mellitus, Experimental/complications/enzymology
MH  - Diabetes Mellitus, Type 2/complications/enzymology
MH  - Diabetic Nephropathies/enzymology/pathology/*prevention & control
MH  - Disease Progression
MH  - Drug Evaluation, Preclinical/methods
MH  - Enzyme Inhibitors/therapeutic use
MH  - Epoxide Hydrolases/*antagonists & inhibitors
MH  - Hypertension/complications/*drug therapy/enzymology/pathology
MH  - Insulin/blood
MH  - Lauric Acids/*therapeutic use/urine
MH  - Lipids/blood
MH  - Male
MH  - NF-kappa B/metabolism
MH  - Rats
MH  - Rats, Inbred Strains
PMC - PMC2590620
MID - NIHMS55919
EDAT- 2008/05/08 09:00
MHDA- 2009/02/21 09:00
PMCR- 2010/01/01
CRDT- 2008/05/08 09:00
PHST- 2008/05/08 09:00 [pubmed]
PHST- 2009/02/21 09:00 [medline]
PHST- 2008/05/08 09:00 [entrez]
PHST- 2010/01/01 00:00 [pmc-release]
AID - CS20080039 [pii]
AID - 10.1042/CS20080039 [doi]
PST - ppublish
SO  - Clin Sci (Lond). 2009 Jan;116(1):61-70. doi: 10.1042/CS20080039.