Effects of exogenous sphinganine, sphingosine, and sphingosine-1-phosphate on relaxation and contraction of porcine thoracic aortic and pulmonary arterial rings.
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 microM) and sphingosine (1.4 microM). 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 un-contracted and phenylephrine-contracted aortic rings at > or = 10 microM and > or = 1 microM, respectively. Sphingosine (> or = 10 microM) relaxed un-contracted and phenylephrine-contracted pulmonary arterial rings, whereas sphingosine-1-phosphate (10 microM) contracted pulmonary arterial rings. Sphingosine (3 microM) 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.
Hsiao
Shih-Hsuan
SH
Department of Veterinary Pathobiology College of Veterinary Medicine, University of Illinois at Urbana-Champaign, Urbana, Illinois 61802, USA. shsiao1@uiuc.edu
Constable
Peter D
PD
Smith
Geoffrey W
GW
Haschek
Wanda M
WM
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D008246:Lysophospholipids / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D010656:Phenylephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011651:Pulmonary Artery / Q000187:drug effects / Q000502:physiology; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D013552:Swine
D008246:Lysophospholipids; D010656:Phenylephrine; C060506:sphingosine 1-phosphate; D011189:Potassium Chloride; D013110:Sphingosine; C005682:safingol