PMID- 9283697
OWN - NLM
STAT- MEDLINE
DCOM- 19980105
LR  - 20161124
IS  - 0007-1188 (Print)
IS  - 0007-1188 (Linking)
VI  - 121
IP  - 8
DP  - 1997 Aug
TI  - Differential effect of L-NAME and S-methyl-isothiourea on leukocyte emigration in 
      carrageenin-soaked sponge implants in rat.
PG  - 1637-44
AB  - 1. The role of nitric oxide (NO) in leukocyte (polymorphonuclear cells, monocytes 
      and lymphocytes) emigration was studied in a model of carrageenin-sponge implants 
      in rats. 2. The subcutaneous implantation of 1% (w/v) of 
      lambda-carrageenin-soaked sponges elicited an inflammatory response that was 
      characterized by a time-related increase in leukocyte infiltration in the sponges 
      and increased levels of nitrite in the exudate. Total leukocyte infiltration and 
      nitrite production were maximal at 24 h and decreased after 48 and 96 h. The 
      mononuclear cell influx was maximal at 48 h (21% of the total leukocytes). 
      Therefore, this time point was used in the successive experiments. 3. 
      Polymorphonuclear cell (PMN) and lymphocyte infiltration in the sponges 
      significantly increased when rats were treated with the non-specific NO-synthase 
      (NOS) inhibitor, NG-nitro-L-arginine methylester (L-NAME) (1 mg ml-1) in drinking 
      water ad libitum). Monocyte emigration was not affected by L-NAME treatment. The 
      nitrite levels in the exudate of L-NAME-treated rats were significantly reduced. 
      The concomitant ingestion of L-arginine (30 mg ml-1) resulted in a reversion of 
      the L-NAME effect, while D-arginine (30 mg ml-1) had no effect, indicating the 
      involvement of the L-arginine: NO pathway. 4. Administration of L-NAME resulted 
      also in an increased release of tumour necrosis factor-alpha (TNF-alpha) and 
      prostacyclin (measured as the stable metabolite, 6-keto-PGF 1 alpha). L-NAME had 
      no effect on monocyte chemoattractant protein-1 (MCP-1) release in the exudate. 
      5. Since L-NAME may have effects on the local blood flow, phenylephrine (0.034 mg 
      ml-2) in drinking water) was used as it has an effect on the local blood flow 
      similar to L-NAME. Phenylephrine had no effect on either leukocyte emigration, or 
      on nitrite, TNF-alpha, prostacyclin or MCP-1 accumulation in the exudate. 6. In 
      contrast, the more selective iNOS inhibitor S-methyl-isothiourea (SMT) (10 
      micrograms ml-1) in drinking water) significantly reduced PMNs and lymphocyte 
      influx in the sponge having no effect on monocyte influx. Moreover, SMT decreased 
      nitrite production in the exudate to a comparable extent as L-NAME. 7. 
      Administration of SMT significantly reduced MCP-1 release in the exudate, without 
      an effect on TNF-alpha or prostacyclin production. Moreover SMT did not produce 
      any changes in local blood flow. 8. Our results show that a different outcome of 
      the inflammatory process can be obtained depending on the types of NOS inhibitor 
      used.
FAU - Iuvone, T
AU  - Iuvone T
AD  - Division of Pharmacology, Faculty of Medicine, University of Antwerpen (UIA), 
      Belgium.
FAU - Van Osselaer, N
AU  - Van Osselaer N
FAU - D'Acquisto, F
AU  - D'Acquisto F
FAU - Carnuccio, R
AU  - Carnuccio R
FAU - Herman, A G
AU  - Herman AG
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Br J Pharmacol
JT  - British journal of pharmacology
JID - 7502536
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Nitrites)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 22584-04-9 (Isothiuronium)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 9000-07-1 (Carrageenan)
RN  - 94ZLA3W45F (Arginine)
RN  - DCR9Z582X0 (Epoprostenol)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase)
RN  - ES8C3884JW (S-methylisothiopseudouronium)
RN  - V55S2QJN2X (NG-Nitroarginine Methyl Ester)
SB  - IM
MH  - Animals
MH  - Arginine/pharmacology
MH  - Capillary Permeability/drug effects
MH  - Carrageenan
MH  - Cell Movement/drug effects
MH  - Enzyme Inhibitors/*pharmacology
MH  - Epoprostenol/biosynthesis
MH  - Inflammation/*blood
MH  - Isothiuronium/*analogs & derivatives/pharmacology
MH  - Leukocytes/*drug effects/physiology
MH  - Male
MH  - NG-Nitroarginine Methyl Ester/*pharmacology
MH  - Nitric Oxide/*physiology
MH  - Nitric Oxide Synthase/*antagonists & inhibitors
MH  - Nitrites/metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Tumor Necrosis Factor-alpha/biosynthesis
PMC - PMC1564873
EDAT- 1997/08/01 00:00
MHDA- 1997/08/01 00:01
PMCR- 1998/08/01
CRDT- 1997/08/01 00:00
PHST- 1997/08/01 00:00 [pubmed]
PHST- 1997/08/01 00:01 [medline]
PHST- 1997/08/01 00:00 [entrez]
PHST- 1998/08/01 00:00 [pmc-release]
AID - 0701317 [pii]
AID - 10.1038/sj.bjp.0701317 [doi]
PST - ppublish
SO  - Br J Pharmacol. 1997 Aug;121(8):1637-44. doi: 10.1038/sj.bjp.0701317.