PMID- 10560940
OWN - NLM
STAT- MEDLINE
DCOM- 19991130
LR  - 20191103
IS  - 0022-2143 (Print)
IS  - 0022-2143 (Linking)
VI  - 134
IP  - 5
DP  - 1999 Nov
TI  - Time course of lipopolysaccharide-induced nitric oxide synthase mRNA expression 
      in rat glomeruli.
PG  - 471-7
AB  - The decrease in glomerular filtration rate that is characteristic of sepsis has 
      been shown to result from the local glomerular inhibition of endothelial nitric 
      oxide synthase (NOS) by nitric oxide (NO) generated from the inducible isoform of 
      NOS (iNOS). iNOS activation depends on de novo synthesis of both RNA and protein. 
      Therefore it is assumed that several hours are required for its full activation. 
      Yet the renal hemodynamic response in sepsis has been documented as early as 60 
      minutes after lipopolysaccharide (LPS) administration. Experiments were designed 
      to determine the time course of LPS-induced glomerular iNOS mRNA expression and 
      activity in rats. Rats were treated with LPS (2 mg/kg body weight IP). Kidneys 
      were removed after 1,2, 4, 6, and 16 hours. Glomeruli were isolated and 
      incubated. Nitric oxide generation was measured with a Griess assay, and iNOS 
      mRNA was studied by reverse transcriptase-polymerase chain reaction. Similar time 
      course experiments were repeated in glomeruli isolated from normal rats and 
      exposed to LPS in vitro. A significant increase in iNOS mRNA expression was 
      evident as early as 60 minutes after both in vivo and in vitro administration of 
      LPS. The quantity of iNOS mRNA reached its peak between 2 to 4 hours after 
      administration and declined to baseline levels after 16 hours. 
      Immunohistochemical studies were remarkable for a significant increase in the 
      staining for iNOS in glomeruli 2 hours after the in vivo administration of LPS. 
      Plasma nitric oxide concentration after the in vivo administration of LPS 
      increased from a baseline level of 11.25 +/- 0.8 micromol/L to a peak level of 
      62.9 +/- 3.8 micromol/L (P < .05 vs baseline) at 4 hours and then decreased to 
      17.5 +/-1.9 micromol/L at 16 hours. Similar results were obtained when the 
      glomerular generation of nitric oxide after in vivo administration of LPS was 
      measured (2.6 +/- 0.8 pmol/h/microg tissue, 17.2 +/- 2.1 pmol/h/microg tissue (P 
      < .05 vs baseline), and 0.4 +/- 0.65 pmol/h/microg tissue, respectively). These 
      results provide evidence of the rapid activation of glomerular iNOS after in vivo 
      and ex vivo administration of LPS and thus support the role of nitric oxide in 
      the early renal hemodynamic response to LPS.
FAU - Sade, K
AU  - Sade K
AD  - Department of Nephrology, Ichilov Hospital, Tel Aviv Sourasky Medical Center, 
      Israel.
FAU - Schwartz, D
AU  - Schwartz D
FAU - Wolman, Y
AU  - Wolman Y
FAU - Schwartz, I
AU  - Schwartz I
FAU - Chernichovski, T
AU  - Chernichovski T
FAU - Blum, M
AU  - Blum M
FAU - Brazowski, E
AU  - Brazowski E
FAU - Keynan, S
AU  - Keynan S
FAU - Raz, I
AU  - Raz I
FAU - Blantz, R C
AU  - Blantz RC
FAU - Iaina, A
AU  - Iaina A
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Lab Clin Med
JT  - The Journal of laboratory and clinical medicine
JID - 0375375
RN  - 0 (DNA Primers)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (RNA, Messenger)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
RN  - EC 1.14.13.39 (Nos2 protein, rat)
SB  - IM
MH  - Animals
MH  - Base Sequence
MH  - DNA Primers/genetics
MH  - Gene Expression/drug effects
MH  - Glomerular Filtration Rate/genetics/physiology
MH  - Immunohistochemistry
MH  - In Vitro Techniques
MH  - Kidney Glomerulus/*drug effects/*enzymology
MH  - Kinetics
MH  - Lipopolysaccharides/*toxicity
MH  - Male
MH  - Nitric Oxide Synthase/*genetics/metabolism
MH  - Nitric Oxide Synthase Type II
MH  - RNA, Messenger/*genetics/*metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Sepsis/genetics/physiopathology
EDAT- 1999/11/24 00:00
MHDA- 1999/11/24 00:01
CRDT- 1999/11/24 00:00
PHST- 1999/11/24 00:00 [pubmed]
PHST- 1999/11/24 00:01 [medline]
PHST- 1999/11/24 00:00 [entrez]
AID - S0022-2143(99)90168-3 [pii]
AID - 10.1016/s0022-2143(99)90168-3 [doi]
PST - ppublish
SO  - J Lab Clin Med. 1999 Nov;134(5):471-7. doi: 10.1016/s0022-2143(99)90168-3.