Endogenously synthesized nitric oxide prevents endotoxin-induced glomerular thrombosis

Pamela J. Shultz, Leopoldo Raij

Research output: Contribution to journalArticle

269 Citations (Scopus)

Abstract

Escherichia coli endotoxin (LPS) can induce the clinical syndrome of septic shock and renal cortical necrosis and can stimulate nitric oxide (NO) production from macrophages, vascular smooth muscle, and glomerular mesangial cells in vitro. NO is an endogenous vasodilator, which also inhibits platelet aggregation and adhesion. We therefore sought to determine whether LPS would stimulate NO production in vivo and, if so, whether this NO would modulate endotoxin-induced glomerular thrombosis. The stable NO endproducts, NO2 and NO3, were measured in serum and urine collections from rats during baseline and after injection of LPS, with or without substances that modulate NO synthesis. The urinary excretion of NO2/NO3 was 1,964±311 nm/8 h during the baseline and increased to 6,833±776 nm/8 h after a single intraperitoneal injection of 0.1 mg/kg LPS (P < 0.05). The serum concentration of NO2/ NO3 also significantly increased after LPS injection. Both the urine and serum stimulation was significantly prevented by the NO synthesis inhibitor, Nw-nitro-L-arginine methyl ester (L-NAME). L-Arginine, given with LPS + L-NAME significantly restored the NO2/NO3 levels in the urine. Ex vivo incubation of tissues from rats treated with LPS demonstrated NO production by the aorta, whole kidney, and glomeruli, but not cortical tubules. Histological examination of kidneys from rats given either LPS or L-NAME alone revealed that 2 and 4.5% of the glomeruli contained capillary thrombosis, respectively. In contrast, rats given LPS + L-NAME developed thrombosis in 55% of glomeruli (P < 0.001), which was significantly prevented when L-arginine was given concomitantly. We conclude that LPS stimulates endogenous production of NO in vivo and that this NO is critical in preventing LPS-induccd renal thrombosis.

Original languageEnglish
Pages (from-to)1718-1725
Number of pages8
JournalJournal of Clinical Investigation
Volume90
Issue number5
StatePublished - Nov 1 1992
Externally publishedYes

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Endotoxins
Nitric Oxide
Thrombosis
NG-Nitroarginine Methyl Ester
Arginine
Kidney Cortex Necrosis
Serum
Kidney Glomerulus
Urine
Kidney
Urine Specimen Collection
Injections
Mesangial Cells
Septic Shock
Intraperitoneal Injections
Vasodilator Agents
Platelet Aggregation
Vascular Smooth Muscle
Aorta
Macrophages

Keywords

  • Cortical necrosis
  • Cyclic 3′,5′-guanosine monophosphate
  • Fibrin
  • Nitrate
  • Nitrite

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Endogenously synthesized nitric oxide prevents endotoxin-induced glomerular thrombosis. / Shultz, Pamela J.; Raij, Leopoldo.

In: Journal of Clinical Investigation, Vol. 90, No. 5, 01.11.1992, p. 1718-1725.

Research output: Contribution to journalArticle

Shultz, Pamela J. ; Raij, Leopoldo. / Endogenously synthesized nitric oxide prevents endotoxin-induced glomerular thrombosis. In: Journal of Clinical Investigation. 1992 ; Vol. 90, No. 5. pp. 1718-1725.
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abstract = "Escherichia coli endotoxin (LPS) can induce the clinical syndrome of septic shock and renal cortical necrosis and can stimulate nitric oxide (NO) production from macrophages, vascular smooth muscle, and glomerular mesangial cells in vitro. NO is an endogenous vasodilator, which also inhibits platelet aggregation and adhesion. We therefore sought to determine whether LPS would stimulate NO production in vivo and, if so, whether this NO would modulate endotoxin-induced glomerular thrombosis. The stable NO endproducts, NO2 and NO3, were measured in serum and urine collections from rats during baseline and after injection of LPS, with or without substances that modulate NO synthesis. The urinary excretion of NO2/NO3 was 1,964±311 nm/8 h during the baseline and increased to 6,833±776 nm/8 h after a single intraperitoneal injection of 0.1 mg/kg LPS (P < 0.05). The serum concentration of NO2/ NO3 also significantly increased after LPS injection. Both the urine and serum stimulation was significantly prevented by the NO synthesis inhibitor, Nw-nitro-L-arginine methyl ester (L-NAME). L-Arginine, given with LPS + L-NAME significantly restored the NO2/NO3 levels in the urine. Ex vivo incubation of tissues from rats treated with LPS demonstrated NO production by the aorta, whole kidney, and glomeruli, but not cortical tubules. Histological examination of kidneys from rats given either LPS or L-NAME alone revealed that 2 and 4.5{\%} of the glomeruli contained capillary thrombosis, respectively. In contrast, rats given LPS + L-NAME developed thrombosis in 55{\%} of glomeruli (P < 0.001), which was significantly prevented when L-arginine was given concomitantly. We conclude that LPS stimulates endogenous production of NO in vivo and that this NO is critical in preventing LPS-induccd renal thrombosis.",
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