PMID- 15951402
OWN - NLM
STAT- MEDLINE
DCOM- 20051128
LR  - 20131121
IS  - 0022-3565 (Print)
IS  - 0022-3565 (Linking)
VI  - 315
IP  - 1
DP  - 2005 Oct
TI  - Early and sustained inhibition of nuclear factor-kappaB prevents hypertension in 
      spontaneously hypertensive rats.
PG  - 51-7
AB  - Compelling evidence has emerged pointing to the interaction of oxidative stress 
      and renal interstitial inflammation and their mutual contribution to the 
      pathogenesis of hypertension in experimental animals. Renal interstitial 
      inflammation in spontaneously hypertensive rats (SHR) is accompanied by and 
      largely due to activation of redox-sensitive, proinflammatory nuclear 
      transcription factor-kappaB (NF-kappaB). Therefore, the present study was 
      designed to test the hypothesis that long-term inhibition of NF-kappaB, beginning 
      early in the course of the disease, may attenuate renal interstitial inflammation 
      and hypertension in SHR. To this end, we administered the reputed NF-kappaB 
      inhibitor pyrrolidine dithiocarbamate (PDTC) (100 mg/kg daily intraperitoneally) 
      to SHR from 7 to 25 weeks of age and compared the results with vehicle-treated 
      SHR. Vehicle-treated and PDTC-treated Wistar Kyoto (WKY) rats served as controls. 
      The untreated SHR exhibited a significant rise in arterial pressure; increased 
      NF-kappaB activation, elevated intercellular adhesion molecule (ICAM)-1 and in 
      situ mRNA macrophage chemoattractant molecule-1 (MCP-1) expressions; and 
      interstitial accumulation of lymphocytes, macrophages, and 
      angiotensin-II-positive cells. PDTC administration prevented the rise in blood 
      pressure, and normalized renal cortical NF-kappaB activity as well as ICAM-1 and 
      MCP-1 expressions. This was accompanied by a significant reduction in 
      infiltration of immune cells, angiotensin II-expressing cells, and renal tissue 
      malondialdehyde content to values that matched those found in the control WKY 
      rats. Results suggest that NF-kappaB-driven intrarenal inflammatory reactivity 
      play a major role in the pathogenesis of hypertension in the SHR.
FAU - Rodriguez-Iturbe, Bernardo
AU  - Rodriguez-Iturbe B
AD  - Renal Service, Hospital Universitario, Universidad del Zulia, Instituto de 
      Investigaciones Biomedicas, Maracaibo, Venezuela. bernardori@telcel.net.ve
FAU - Ferrebuz, Atilio
AU  - Ferrebuz A
FAU - Vanegas, Valentina
AU  - Vanegas V
FAU - Quiroz, Yasmir
AU  - Quiroz Y
FAU - Mezzano, Sergio
AU  - Mezzano S
FAU - Vaziri, Nosratola D
AU  - Vaziri ND
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20050610
PL  - United States
TA  - J Pharmacol Exp Ther
JT  - The Journal of pharmacology and experimental therapeutics
JID - 0376362
RN  - 0 (Ccl2 protein, rat)
RN  - 0 (Chemokine CCL2)
RN  - 0 (NF-kappa B)
RN  - 0 (Thiocarbamates)
RN  - 11128-99-7 (Angiotensin II)
RN  - 126547-89-5 (Intercellular Adhesion Molecule-1)
RN  - 135467-92-4 (prolinedithiocarbamate)
RN  - 9DLQ4CIU6V (Proline)
SB  - IM
MH  - Angiotensin II/analysis
MH  - Animals
MH  - Blood Pressure/drug effects
MH  - Body Weight/drug effects
MH  - Chemokine CCL2/analysis
MH  - Hypertension/pathology/physiopathology/*prevention & control
MH  - Intercellular Adhesion Molecule-1/analysis
MH  - Male
MH  - NF-kappa B/*antagonists & inhibitors/physiology
MH  - Proline/*analogs & derivatives/therapeutic use
MH  - Rats
MH  - Rats, Inbred SHR
MH  - Rats, Inbred WKY
MH  - Thiocarbamates/*therapeutic use
EDAT- 2005/06/14 09:00
MHDA- 2005/12/13 09:00
CRDT- 2005/06/14 09:00
PHST- 2005/06/14 09:00 [pubmed]
PHST- 2005/12/13 09:00 [medline]
PHST- 2005/06/14 09:00 [entrez]
AID - jpet.105.088062 [pii]
AID - 10.1124/jpet.105.088062 [doi]
PST - ppublish
SO  - J Pharmacol Exp Ther. 2005 Oct;315(1):51-7. doi: 10.1124/jpet.105.088062. Epub 
      2005 Jun 10.