Reduced nitric oxide bioavailability in a baboon model of Shiga toxin mediated hemolytic uremic syndrome (HUS).

Abstract

BACKGROUND:

Although there is agreement that post-diarrheal hemolytic uremic syndrome (D+ HUS) is caused by Shiga toxin (Stx)-producing E. coli, little is known about factors that mediate the host response to these toxins and potentially contribute to pathogenesis. Nitric oxide (NO) is a candidate mediator by virtue of its antiplatelet and renal vasodilatory properties.

METHODS:

We used a baboon model of HUS to measure plasma and urinary NO metabolites and expression of NO synthase (eNOS and iNOS) in renal tissue following the intravenous administration of Stx-1.

RESULTS:

Plasma concentrations through 60 hours of observation did not differ significantly from controls. Urinary values (indexed against urinary creatinine) tended, however, to rise during the initial 12 hours following administration of Stx-1. This was followed by a sustained reduction that coincided with the development of hemolytic anemia (schistocytosis) and other features of HUS. However, immunohistochemical staining for eNOS and iNOS in tissue obtained immediately after death at a median of 59 hours showed similar levels in control and Stx-treated animals, despite the presence of a florid thrombotic microangiopathy and tubular injury in the Stx-treated group.

CONCLUSION:

We propose that urinary NO metabolite reduction was due to NO inactivation subsequent to its avid binding to free hemoglobin released from lysed red blood cells, and that this contributed to the acute renal failure by facilitating vasoconstriction and platelet aggregation and adhesion within the renal microvasculature.

• Authors: Richard L Siegler, Theodore J Pysher, Vernon L Tesh, Marina Noris, Paola Cassis, Fletcher B Taylor Jr
• Journal: Renal failure (Ren Fail) Vol. 27 Issue 5 Pg. 635-41 ( 2005) ISSN: 0886-022X [Print] England
• PMID: 16153006 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Nitric Oxide
• Shiga Toxin
• Nitric Oxide Synthase

Topics

• Animals
• Blood Chemical Analysis
• Disease Models, Animal
• Hemolytic-Uremic Syndrome (enzymology, physiopathology)
• Nitric Oxide (metabolism)
• Nitric Oxide Synthase (analysis, metabolism)
• Papio
• Reference Values
• Risk Factors
• Sensitivity and Specificity
• Shiga Toxin
• Urinalysis