Renal Prostacyclin Biosynthesis in a Baboon Model of Shiga Toxin Mediated Hemolytic Uremic Syndrome

Autor: Richard L. Siegler, Vernon L. Tesh, Theodore J. Pysher, Fletcher B. Taylor
Rok vydání: 2002
Předmět:
Zdroj: Nephron. 92:363-368
ISSN: 2235-3186
1660-8151
DOI: 10.1159/000063310
Popis: Background/Aims: Shiga toxin (Stx) and lipopolysaccharide (LPS) both participate in the pathogenesis of post-diarrheal (D+) hemolytic uremic syndrome (HUS), but little is known about factors that modulate the host response to these toxins. Prostacyclin (PGI2) is a potent renal vasodilator and inhibitor of platelet aggregation and adhesion. An inability to produce PGI2 in response to endothelial cell injury could drive the pathogenic cascade. We therefore used a baboon model of HUS to measure PGI2 production following the administration of Stx and LPS. Methods: Shiga toxin-1 (Stx-1), with and without LPS, was administered intravenously to baboons in various doses and schedules. 6-keto-PGF1α, the stable metabolite of PGI2, was measured by ELISA in the plasma and urine. Results: Plasma concentrations did not change significantly. Urine values increased significantly in some groups, but not in others, and HUS developed both in animals that did and did not exhibit a significant increase in urinary PGI2 production. Conclusions: Renal PGI2 biosynthesis appears to be affected by the dose and rate of Stx administration, and the timing of LPS infusion. PGI2 does not protect our primate model from developing HUS.
Databáze: OpenAIRE