(The FASEB Journal. 2008;22:743.5)
© 2008 FASEB
(The FASEB Journal. 2008;22:743.5.)
© 2008 FASEB
Inhibiting vascular ceramide synthesis prevents arterial dysfunction and hypertension in mice with diet-induced obesity
J. David Symons1,2,
William Holland2,
Jason Tanner1,
Devin Kearns1,
Judd Cahoon1,
Milda Palionyte1,
Bradlee Duncan1,
Jason Losee1,
Krishna Narra2,
Elaine Hillas3,
Andreas Rohrwasser3,
E. Dale Abel2 and
Scott Summers2
1 College of Health
2 Endocrinology, Metabolism, and Diabetes
3 Genetics, University of Utah, Salt Lake City, UT
ABSTRACT
Ceramide accumulation in vascular smooth muscle might contribute to obesity-related arterial dysfunction and hypertension. To test this hypothesis, mice were treated with myriocin (M), an inhibitor of an enzyme required for ceramide biosynthesis (i.e., serine palmitoyltransferase). 10-week old mice consumed chow containing 45% (HF, n=20) or 10% (Con, n=20) fat ± M (0.3 mg/kg i.p., n=10) or vehicle (V; saline i.p., n=10) for 14 weeks. Mean (MAP), systolic (SBP), and diastolic (DBP) blood pressures then were recorded via telemetry for 6 x 24-h periods followed by excision of the aorta and femoral arteries. Vascular ceramide (pmol ceramide/mg aorta) increased (p<0.05) from 17±4 in Con-V mice to 30±3 in HF-V animals, and was suppressed in HF-M animals (10±1). Elevated (*p<0.05) MAP, SBP, and DBP in HF-V vs. Con-V mice was prevented in HF-M animals. Values in the Table represent the mean±SE of 6 dark/active cycles. Impaired (*p<0.05) acetylcholine (ACh)-evoked vasorelaxation (wire-myography) in femoral arteries from HF-V vs. Con-V mice was prevented in HF-M animals. Sodium-nitroprusside-evoked vasorelaxation was similar among groups. ACh values represent % vasorelaxation.
These results suggest that vascular ceramide accumulation may contribute to arterial dysfunction and hypertension in mice with diet-induced obesity. AHA GIA 06-55222Y
