Aspirin protected the nitric oxide/cyclic GMP generating system in human peritoneum.
OBJECTIVE
Changes in the expression of endothelial nitric oxide synthase (eNOS) in the peritoneum could be involved in the peritoneal dysfunction associated with peritoneal inflammation. The aim of the present study was to analyze the effect of Escherichia coli lipopolysaccharide (LPS) on eNOS expression in samples of human peritoneum. The effect of aspirin, a drug with anti-inflammatory properties, was also determined.


RESULTS
The eNOS protein expressed in human peritoneal tissue was reduced by LPS (10 microg/mL) in a time-dependent manner. The eNOS was expressed mainly in capillary endothelial cells and mesothelial cells. Anti-inflammatory doses of aspirin (1-10 mmol/L) restored eNOS expression in LPS-stimulated human peritoneal tissue samples. The main intracellular receptor of NO, soluble guanylate cyclase (sGC), was also downregulated by LPS. This effect was prevented by aspirin (5 mmol/L).


CONCLUSIONS
Protein expression of the eNOS-sGC system in the peritoneal tissue was downregulated by LPS. High doses of aspirin protected both eNOS protein expression and sGC in human peritoneum. These findings suggest a new mechanism of action of aspirin that could be involved in the prevention of peritoneal dysfunction during inflammation.
Arriero
M M
MM
Cardiovascular Research and Hypertension Laboratory, Fundación Jiménez Díaz, Madrid, Spain.
Celdran
A
A
Jimenez
P
P
García-Mendez
A
A
de la Pinta
J C
JC
Manzarbeitia
F
F
Muñoz-Alameda
L
L
Reyero
A
A
Escribano
M
M
Casado
S
S
López-Farré
A
A
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001241:Aspirin / Q000494:pharmacology*; D015153:Blotting, Western; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004926:Escherichia coli; D006162:Guanylate Cyclase / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008070:Lipopolysaccharides; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D010537:Peritoneum / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D000071756:Soluble Guanylyl Cyclase
D000894:Anti-Inflammatory Agents, Non-Steroidal; D008070:Lipopolysaccharides; D018160:Receptors, Cytoplasmic and Nuclear; D009569:Nitric Oxide; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D006162:Guanylate Cyclase; D000071756:Soluble Guanylyl Cyclase; D006152:Cyclic GMP; D001241:Aspirin