Glomerular and vascular tissues do not down-regulate nitric oxide synthesis during protracted endotoxemia

Domingo Del Castillo, Anupam Agarwal, Edgar A. Jaimes, Leopoldo Raij

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Down-regulation of cytokines is implicated as an important component of the phenomenon of tolerance to bacterial products in humans and animals. Since many effects of endotoxin and cytokines are mediated by nitric oxide, this study was designed to evaluate in vivo the L-arginine:NO pathway in endotoxin tolerance. Sublethal injections of E. coli lipopolysaccharide (LPS, 1 mg/kg body wt, i.p.) were given to rats daily for five days. Blood levels of NO2-/NO3-, stable metabolites of nitric oxide (NO), significantly increased on day 1 (baseline, 89.64 ± 40, day 1, 260.32 ± 36 nmol/ml; P < 0.05) but returned to baseline levels on day 5 (77.60 ± 5 nmol/ml). However, urinary NO2-/NO3- remained significantly elevated several-fold throughout the study period (baseline, 121.25 ± 11.4, day 1, 899.35 ± 15.8, day 5, 250.23 ± 21.4 nmol/hr/100 g body wt). Glomeruli and aortae obtained from these rats showed increased NO production that was maintained at similar levels even at day 5 (glomeruli: control, 0.01 ± 0.0, day 1, 22.4 ± 0.3, and day 5, 22.0 ± 2.5, P < 0.05 vs. control; aortae: control, 0.01 ± 0.0, day 1, 4.3 ± 2.2, and day 5, 5.4 ± 1.0 nmol/hr/mg protein, P < 0.05 vs. control, respectively); this further increased significantly in response to in vitro LPS challenge. However, peritoneal macrophages, liver and spleen showed an initial increase in NO production that decreased significantly by the fifth day of LPS and could not be further stimulated by in vitro LPS challenge. Thus, in vivo NO synthesis is down-regulated during protracted LPS. Our results show that the process is relatively specific to the liver, spleen and macrophages, and is qualitatively and quantitatively different in vascular tissues such as aortae and glomeruli.

Original languageEnglish
Pages (from-to)460-467
Number of pages8
JournalKidney International
Volume52
Issue number2
StatePublished - Sep 8 1997
Externally publishedYes

Fingerprint

Endotoxemia
Blood Vessels
Nitric Oxide
Down-Regulation
Aorta
Endotoxins
Spleen
Cytokines
Liver
Peritoneal Macrophages
Lipopolysaccharides
Arginine
Macrophages
Escherichia coli
Injections
Proteins

Keywords

  • Endothelium
  • Endotoxin
  • Inflammation
  • Nitric oxide
  • Sepsis
  • Tumor necrosis factor

ASJC Scopus subject areas

  • Nephrology

Cite this

Del Castillo, D., Agarwal, A., Jaimes, E. A., & Raij, L. (1997). Glomerular and vascular tissues do not down-regulate nitric oxide synthesis during protracted endotoxemia. Kidney International, 52(2), 460-467.

Glomerular and vascular tissues do not down-regulate nitric oxide synthesis during protracted endotoxemia. / Del Castillo, Domingo; Agarwal, Anupam; Jaimes, Edgar A.; Raij, Leopoldo.

In: Kidney International, Vol. 52, No. 2, 08.09.1997, p. 460-467.

Research output: Contribution to journalArticle

Del Castillo, D, Agarwal, A, Jaimes, EA & Raij, L 1997, 'Glomerular and vascular tissues do not down-regulate nitric oxide synthesis during protracted endotoxemia', Kidney International, vol. 52, no. 2, pp. 460-467.
Del Castillo, Domingo ; Agarwal, Anupam ; Jaimes, Edgar A. ; Raij, Leopoldo. / Glomerular and vascular tissues do not down-regulate nitric oxide synthesis during protracted endotoxemia. In: Kidney International. 1997 ; Vol. 52, No. 2. pp. 460-467.
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