TY - JOUR
T1 - Hypertension Is Associated with Marked Alterations in Sphingolipid Biology: A Potential Role for Ceramide
AU - Spijkers, Leon J. A.
AU - van den Akker, Rob F. P.
AU - Janssen, Ben J. A.
AU - Debets, Jacques J.
AU - De Mey, Jo G. R.
AU - Stroes, Erik S. G.
AU - van den Born, Bert-Jan H.
AU - Wijesinghe, Dayanjan S.
AU - Chalfant, Charles E.
AU - MacAleese, Luke
AU - Eijkel, Gert B.
AU - Heeren, Ron M. A.
AU - Alewijnse, Astrid E.
AU - Peters, Stephan L. M.
PY - 2011/7/19
Y1 - 2011/7/19
N2 - Background: Hypertension is, amongst others, characterized by endothelial dysfunction and vascular remodeling. As sphingolipids have been implicated in both the regulation of vascular contractility and growth, we investigated whether sphingolipid biology is altered in hypertension and whether this is reflected in altered vascular function. Methods and Findings: In isolated carotid arteries from spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats, shifting the ceramide/S1P ratio towards ceramide dominance by administration of a sphingosine kinase inhibitor (dimethylsphingosine) or exogenous application of sphingomyelinase, induced marked endothelium-dependent contractions in SHR vessels (DMS: 1.4 +/- 0.4 and SMase: 2.1 +/- 0.1 mN/mm; n = 10), that were virtually absent in WKY vessels (DMS: 0.0 +/- 0.0 and SMase: 0.6 +/- 0.1 mN/mm; n = 9, p
AB - Background: Hypertension is, amongst others, characterized by endothelial dysfunction and vascular remodeling. As sphingolipids have been implicated in both the regulation of vascular contractility and growth, we investigated whether sphingolipid biology is altered in hypertension and whether this is reflected in altered vascular function. Methods and Findings: In isolated carotid arteries from spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats, shifting the ceramide/S1P ratio towards ceramide dominance by administration of a sphingosine kinase inhibitor (dimethylsphingosine) or exogenous application of sphingomyelinase, induced marked endothelium-dependent contractions in SHR vessels (DMS: 1.4 +/- 0.4 and SMase: 2.1 +/- 0.1 mN/mm; n = 10), that were virtually absent in WKY vessels (DMS: 0.0 +/- 0.0 and SMase: 0.6 +/- 0.1 mN/mm; n = 9, p
U2 - 10.1371/journal.pone.0021817
DO - 10.1371/journal.pone.0021817
M3 - Article
C2 - 21818267
SN - 1932-6203
VL - 6
SP - 9
JO - PLOS ONE
JF - PLOS ONE
IS - 7
ER -