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ToxSci Advance Access originally published online on April 13, 2005
Toxicological Sciences 2005 86(1):194-199; doi:10.1093/toxsci/kfi167
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© The Author 2005. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oupjournals.org

Effects of Exogenous Sphinganine, Sphingosine, and Sphingosine-1-Phosphate on Relaxation and Contraction of Porcine Thoracic Aortic and Pulmonary Arterial Rings

Shih-Hsuan Hsiao*,1, Peter D. Constable{dagger}, Geoffrey W. Smith*,{dagger} and Wanda M. Haschek*

* Department of Veterinary Pathobiology College of Veterinary Medicine, University of Illinois at Urbana-Champaign, Urbana, Illinois 61802, USA and {dagger} Department of Veterinary Clinical Medicine, College of Veterinary Medicine, University of Illinois at Urbana-Champaign, Urbana, Illinois 61802

Received February 9, 2005; accepted April 1, 2005

Fumonisin mycotoxicosis in pigs causes a decrease in mean aortic pressure, an increase in mean pulmonary arterial pressure, and increases in serum concentrations of sphinganine (3.2 µM) and sphingosine (1.4 µM). To determine a causal relationship between the hemodynamic changes and sphingolipid alterations, we examined the in vitro effects of sphinganine, sphingosine, and sphingosine-1-phosphate on porcine aortic and pulmonary arterial rings. Both sphinganine and sphingosine relaxed uncontracted and phenylephrine-contracted aortic rings at ≥10 µM and ≥1 µM, respectively. Sphingosine (≥10 µM) relaxed uncontracted and phenylephrine-contracted pulmonary arterial rings, whereas sphingosine-1-phosphate (10 µM) contracted pulmonary arterial rings. Sphingosine (3 µM) also impaired the contractile response of pulmonary artery rings to 60 mM KCl. The results suggested that the systemic hypotension caused by fumonisin is mediated, in part, by increases in serum sphinganine and sphingosine concentrations, and the pulmonary hypertension is mediated, in part, by increased sphingosine-1-phosphate concentrations.

Key Words: fumonisin mycotoxicosis; sphinganine; sphingosine; sphingosine-1-phosphate; aortic and pulmonary arterial rings; pigs.


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