Altering sphingomyelin signaling in vessels from stroke-prone spontaneously hypertensive rats

C. S. Tsai, R Clinton Webb, J. S. Jin

Research output: Contribution to journalArticle

Abstract

Background. Ceramide acts as an intracellular second messenger in inhibiting protein kinase C and activating phosphatase. Previous investigators showed ceramide stimulates protein phosphatase and inhibits protein kinase C in culture cells. Our recent results indicate that ceramide is a potent vasorelaxant. It is unclear whether ceramide-induced relaxation is altered in vessels from hypertensive animals. We tested the hypothesis that ceramide regulates vascular reactivity by altering sphingomyelin signaling in vascular smooth muscle of stroke-prone spontaneously hypertensive rats (SHR-SP). Methods and Results. Natural ceramide was applied to phenylephrine precontracted aortic rings from female SHR-SP and Wistar- Kyoto rats KY) in an organ bath. When vessels (endothelium intact) from SHR- SP and WKY were compared, both relaxed equally in response to ceramide. However, in endothelium-denuded vessels, the ceramide-induced relaxation (from 3 x 10-7 to 10-5 mole/L) was significantly larger in SHR-SP when compared to that of WKY. Similar augmentation in relaxation response to ceramide in vessels from SHR-SP was noticed in endothelium-intact aortic rings pretreated with N(ω)-nitro-L-arginine (L-NNA, 10-4 mole/L) or methylene blue (10-5 mole/L). In SHR-SP, removal of the endothelium significantly inhibited ceramide (10-5 M)-induced relaxation, but L-NNA and methylene blue did not significantly inhibit ceramide-induced relaxation. In contrast, ceramide (10-5 mole/L)-induced relaxation in endothelium-intact vessels from WKY was significantly inhibited by removal of endothelium, and by pretreatment with L-NNA or methylene blue. Conclusions. Sphingomyelin signaling may have an important role in regulating vascular tone. The alteration of ceramide-induced relaxation in SHR-SP suggests a pathological change in sphingomyelin signaling may occur during the development of hypertension.

Original languageEnglish (US)
Pages (from-to)194-205
Number of pages12
JournalActa Cardiologica Sinica
Volume14
Issue number4
StatePublished - Dec 1 1998
Externally publishedYes

Fingerprint

Sphingomyelins
Ceramides
Inbred SHR Rats
Stroke
Endothelium
Methylene Blue
Protein Kinase C
Blood Vessels
Inbred WKY Rats
Phosphoprotein Phosphatases
Second Messenger Systems
Phenylephrine
Vasodilator Agents
Baths
Vascular Smooth Muscle
Phosphoric Monoester Hydrolases
Arginine
Cell Culture Techniques

Keywords

  • Ceramide
  • Nitric oxide
  • Sphingomyelin
  • Spontaneously hypertensive rats

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Altering sphingomyelin signaling in vessels from stroke-prone spontaneously hypertensive rats. / Tsai, C. S.; Webb, R Clinton; Jin, J. S.

In: Acta Cardiologica Sinica, Vol. 14, No. 4, 01.12.1998, p. 194-205.

Research output: Contribution to journalArticle

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abstract = "Background. Ceramide acts as an intracellular second messenger in inhibiting protein kinase C and activating phosphatase. Previous investigators showed ceramide stimulates protein phosphatase and inhibits protein kinase C in culture cells. Our recent results indicate that ceramide is a potent vasorelaxant. It is unclear whether ceramide-induced relaxation is altered in vessels from hypertensive animals. We tested the hypothesis that ceramide regulates vascular reactivity by altering sphingomyelin signaling in vascular smooth muscle of stroke-prone spontaneously hypertensive rats (SHR-SP). Methods and Results. Natural ceramide was applied to phenylephrine precontracted aortic rings from female SHR-SP and Wistar- Kyoto rats KY) in an organ bath. When vessels (endothelium intact) from SHR- SP and WKY were compared, both relaxed equally in response to ceramide. However, in endothelium-denuded vessels, the ceramide-induced relaxation (from 3 x 10-7 to 10-5 mole/L) was significantly larger in SHR-SP when compared to that of WKY. Similar augmentation in relaxation response to ceramide in vessels from SHR-SP was noticed in endothelium-intact aortic rings pretreated with N(ω)-nitro-L-arginine (L-NNA, 10-4 mole/L) or methylene blue (10-5 mole/L). In SHR-SP, removal of the endothelium significantly inhibited ceramide (10-5 M)-induced relaxation, but L-NNA and methylene blue did not significantly inhibit ceramide-induced relaxation. In contrast, ceramide (10-5 mole/L)-induced relaxation in endothelium-intact vessels from WKY was significantly inhibited by removal of endothelium, and by pretreatment with L-NNA or methylene blue. Conclusions. Sphingomyelin signaling may have an important role in regulating vascular tone. The alteration of ceramide-induced relaxation in SHR-SP suggests a pathological change in sphingomyelin signaling may occur during the development of hypertension.",
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