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Am J Physiol Heart Circ Physiol 284: H2034-H2044, 2003; doi:10.1152/ajpheart.00155.2002
0363-6135/03 $5.00
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Vol. 284, Issue 6, H2034-H2044, June 2003

Fumonisin-induced blockade of ceramide synthase in sphingolipid biosynthetic pathway alters aortic input impedance spectrum of pigs

Peter D. Constable1,2, Geoffrey W. Smith1,2, George E. Rottinghaus3, Mike E. Tumbleson4, and Wanda M. Haschek2

Departments of 1 Veterinary Clinical Medicine, 2 Veterinary Pathobiology, and 4 Veterinary Biosciences, University of Illinois at Urbana-Champaign, Urbana, Illinois 61802; and 3 Veterinary Medical Diagnostic Laboratory, University of Missouri, Columbia, Missouri 65211

The sphingolipid signaling pathway appears to play an important role in regulating vascular tone. We examined the effect of fumonisin B1, a fungal toxin in corn that blocks ceramide synthase in the sphingolipid signaling pathway, on the ascending aortic impedance spectrum of pigs. Sixteen pigs were fed culture material containing fumonisin B1 (20 mg/kg body wt) (n = 7) or a control diet (n = 9) daily for 3 days and then instrumented under alpha -chloralose anesthesia for measurement of ascending aortic pressure and flow. Fumonisin ingestion increased serum sphinganine and sphingosine concentrations. Fumonisin ingestion also decreased cardiac output and characteristic impedance and increased the frequency of the first minimum impedance modulus, systemic vascular resistance, and the terminal, first, and second harmonic reflection coefficients, without changing mean arterial pressure. Thus blockade of ceramide synthase is accompanied by decreased vascular tone in systemic conduit arteries and increased vascular tone in systemic resistance vessels. The results indicate that the sphingolipid signaling pathway influences vascular tone in alpha -chloralose-anesthetized pigs.

afterload; sphingosine; sphinganine; tumor necrosis factor-alpha


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