title: Regulation of aquaporin-1 and nitric oxide synthase isoforms in a rat model of acute peritonitis.
abstract: The loss of ultrafiltration (UF) that accompanies acute peritonitis is a common problem in peritoneal dialysis (PD). It has been suggested that changes in nitric oxide (NO)-mediated vascular tone and permeability might be involved in the loss of UF, whereas channel-mediated water permeability should not be affected. This study used a model of acute peritonitis in rats to characterize changes in PD parameters, in correlation with: (1) expression studies of water channel aquaporin-1 and NO synthase (NOS) isoforms and (2) enzymatic assays for NOS in the peritoneum. Compared with controls, rats with peritonitis had a higher removal of plasma urea, a faster glucose absorption, and a loss of UF. Additional changes, including high protein loss, elevated leukocyte counts in dialysate, positive bacterial cultures, edema, and mononuclear infiltrates, were similar to those observed in PD patients with acute peritonitis. Acute peritonitis in rats induced a major increase in total NOS activity, which was inversely correlated with free-water permeability. The increased NOS activity was mediated by both inducible (Ca2+-independent) and endothelial (Ca2+-dependent) NOS isoforms and was reflected by increased peritoneal staining for nitrotyrosine. In contrast, aquaporin-1 expression was unchanged in rats with peritonitis. These findings cast light on the pathophysiology of permeability changes and loss of UF that characterize acute peritonitis. In particular, these data suggest that a local production of NO, mediated by different NOS isoforms, might play a key role in these changes.
authors.affiliation: Division of Nephrology, Université Catholique de Louvain, Brussels, Belgium.
authors.forename: S
authors.initials: S
authors.lastname: Combet
authors.forename: M
authors.initials: M
authors.lastname: Van Landschoot
authors.forename: P
authors.initials: P
authors.lastname: Moulin
authors.forename: A
authors.initials: A
authors.lastname: Piech
authors.forename: J M
authors.initials: JM
authors.lastname: Verbavatz
authors.forename: E
authors.initials: E
authors.lastname: Goffin
authors.forename: J L
authors.initials: JL
authors.lastname: Balligand
authors.forename: N
authors.initials: N
authors.lastname: Lameire
authors.forename: O
authors.initials: O
authors.lastname: Devuyst
mesh_terms: D000208:Acute Disease; D000704:Analysis of Variance; D000818:Animals; D051398:Aquaporin 1; D020346:Aquaporins / Q000378:metabolism*; D002199:Capillary Permeability; D004195:Disease Models, Animal; D016228:Endothelial Growth Factors / Q000032:analysis; D007118:Immunoassay; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000378:metabolism; D008222:Lymphokines / Q000032:analysis; D008297:Male; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D010530:Peritoneal Dialysis; D010537:Peritoneum / Q000378:metabolism; D010538:Peritonitis / Q000378:metabolism* / Q000628:therapy; D020033:Protein Isoforms / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D012680:Sensitivity and Specificity; D014443:Tyrosine / Q000031:analogs & derivatives / Q000032:analysis; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
chemical_list: C496022:Aqp1 protein, rat; D020346:Aquaporins; D016228:Endothelial Growth Factors; D007527:Isoenzymes; D008222:Lymphokines; D020033:Protein Isoforms; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D051398:Aquaporin 1; C002744:3-nitrotyrosine; D014443:Tyrosine; D019001:Nitric Oxide Synthase