Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0341503 (bacterial peritonitis)
 1,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nitric oxide (NO) has multiple actions, ranging from immunomodulation to regulation of vascular tone and capillary flow. Thus NO generation within the peritoneum could potentially affect peritoneal transport by increasing capillary vasodilatation, and regulate the response to bacterial invasion. Peritoneal mesothelial cells have a common embryological derivation with endothelial cells. As mesothelial cells are the predominant cell type lining the peritoneal cavity, they could potentially be a major source of locally produced nitric oxide. Nitric oxide was measured using the Griess reaction, as total nitrite and nitrate, in fresh unused and spent dialysate effluent (SPDE) from both healthy peritoneal dialysis patients, and during episodes of bacterial peritonitis. Whereas fresh CAPD dialysate was nitrite free (5 +/- 0.1 microM), SPDE from a standard 4 h day time exchange contained 10.2 +/- 0.6 microM/L/h, and that from the overnight dwell 9.1 +/- 0.7 microM/L/h. During an episode of peritonitis, dialysate nitrite and nitrate increased significantly from 9.0 +/- 1.0 microM/L/h, when not infected to 17.5 +/- 2.4, from the first CAPD bag drained at presentation, and 15.2 +/- 1.8 for the second and 16.0 +/- 2.5 for the third exchange (p<0.01). By the following day nitrite levels had returned to baseline, 7.0 +/- 1.0 microM/L/h. Human peritoneal mesothelial cells (HPMC) were cultured and found to produce nitric oxide (261 nmol/mg cell protein), which increased in a dose dependent manner with the addition of spent uninfected CAPD dialysate. The addition of L-arginine, a NO substrate resulted in a 10% increase in nitric oxide production, whereas the addition of the blocker L-NMMA produced a 10% reduction. RNA for inducible nitric oxide synthase (iNOS) was sought using northern blotting technique following combination stimulation with lipopolysaccharide and cytokines (IL-1beta, TNFalpha and gamma-INF, and/or spent dialysate from patients with bacterial peritonitis). However, we could not demonstrate RNA production for iNOS. Peritoneal mesothelial cells may be an important source of locally generated nitric oxide within the peritoneal cavity under basal conditions, but as they do not contain iNOS, the markedly increased NO production observed with episodes of acute bacterial peritonitis is more likely due to a combination of increased NO production by peritoneal macrophages and endothelial cells.
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PMID:Nitric oxide production by human peritoneal mesothelial cells. 1498 79

Hepatorenal syndrome (HRS), a severe complication of advanced cirrhosis, is defined as hypoperfusion of kidneys resulting from intense renal vasoconstriction in response to generalized systemic arterial vasodilatation. Nevertheless, the mechanisms have been barely investigated. Cumulative studies demonstrated renal vasodilatation in portal hypertensive and compensated cirrhotic rats. Previously, we identified that blunted renal vascular reactivity of portal hypertensive rats was reversed after lipopolysaccharide (LPS). This study was therefore conducted to delineate the sequence of renal vascular alternation and underlying mechanisms in LPS-treated cirrhotic rats. Sprague-Dawley rats were randomly allocated to receive sham surgery (Sham) or common bile duct ligation (CBDL). LPS was induced on the 28th day after surgery. Kidney perfusion was performed at 0.5 or 3 h after LPS to evaluate renal vascular response to endothelin-1 (ET-1). Endotoxemia increased serum ET-1 levels ( P < 0.0001) and renal arterial blood flow ( P < 0.05) in both Sham and CBDL rats. CBDL rats showed enhanced renal vascular reactivity to ET-1 at 3 h after LPS ( P = 0.026). Pretreatment with endothelin receptor type A (ETA) antagonist abrogated the LPS-enhanced renal vascular response in CBDL rats ( P < 0.001). There were significantly lower inducible nitric oxide synthase (iNOS) expression but higher ETA and phosphorylated extracellular signal-regulated kinase (p-ERK) expressions in renal medulla of endotoxemic CBDL rats ( P < 0.05). We concluded that LPS-induced renal iNOS inhibition, ETA upregulation, and subsequent ERK signaling activation may participate in renal vascular hyperreactivity in cirrhosis. ET-1-targeted therapy may be feasible in the control of HRS. NEW & NOTEWORTHY Hepatorenal syndrome (HRS) occurred in advanced cirrhosis after large-volume paracentesis or bacterial peritonitis. We demonstrated that intraperitoneal lipopolysaccharide (LPS) enhanced renal vascular reactivity to endothelin-1 (ET-1) in cirrhotic rats, accompanied by inducible nitric oxide synthase inhibition, endothelin receptor type A (ETA) upregulation, and subsequent extracellular signal-regulated kinase activation in renal medulla. Pretreatment with ETA antagonist abrogated the LPS-enhanced renal vascular response in common bile duct ligation rats. These findings suggest that further clinical investigation of ET-1-targeted therapy may be feasible in the control of HRS.
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PMID:Endotoxemia-enhanced renal vascular reactivity to endothelin-1 in cirrhotic rats. 3009 97