Endothelium-Dependent Contractile Factor Release Is Related To Sphingolipid Alterations In Essential Hypertension (original) (raw)

2010

Abstract

We and others have previously shown that sphingolipids, a family of bioactive membrane lipids, can modulate endothelium-derived relaxing factor signalling. Since hypertension is associated with endothelial dysfunction, we investigated whether hypertension is associated with altered vascular sphingolipid biology and/or sphingolipid levels. In isolated carotid arteries from spontaneously hypertensive rats (SHR), pharmacological modulation of sphingolipid metabolism by means of exogenously applied sphingomyelinase (SMase, 0.1U/ml) or application of the sphingosine kinase inhibitor dimethylsphingosine (DMS, 10μM), induced marked transient contractions (2.1 ± 0.1 mN/mm and 1.4±0.4 mN/mm respectively; n=10). These contractions were virtually absent in vessels from normotensive Wistar Kyoto rats (WKY; 0.6±0.1mN/mm and 0.0±0.0 mN/mm respectively; n=9). Notably, the contractions were fully abolished by prior endothelium removal or by the cyclooxygenase inhibitor indomethacin (10μM; 0.0±0.0 m...

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