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題名 | Altering Sphingomyelin Signaling in Vessels from Stroke-prone Spontaneously Hypertensive Rats=易中風型高血壓鼠的血管改變了鞘髓磷脂的傳遞路徑 |
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作者 | 蔡建松; 金忠孝; | 書刊名 | Acta Cardiologica Sinica |
卷期 | 14:4 民87.10-12 |
頁次 | 頁194-205 |
分類號 | 418.221 |
關鍵詞 | 鞘髓磷脂; 塞落美; 一氧化氮; 易中風型的高血壓鼠; Sphingomyelin; Ceramide; Nitric oxide; Spontaneously hypertensive rats; |
語文 | 英文(English) |
中文摘要 | 背景:塞落美是細胞內的訊息傳遞物,以往學者的研究顯示塞落美可以活化去磷 酸脢及抑制丙型蛋白激脢,我們的結果顯示塞落美具有舒張血管的作用。目前對於塞落美的 舒血管作用在易中風型的高血壓鼠是否改變則是不清楚,引發了我們此篇研究的興趣。 方法與結果:自易中風型的高血壓鼠及正常鼠取得的胸主動脈置於組織槽中記錄收縮張力, 在內皮細胞完整的血管,不論是易中風型的高血壓鼠或正常鼠對塞落美皆引起等幅度的舒張 作用;但是在內皮細胞去除的血管,易中風型的高血壓鼠較正常鼠有較大的舒張作用。同樣 在內皮細胞完整的血管,事先以一氧化氮合成脢抑制劑或鳥嘌呤核酸環化脢抑制劑處理,則 易中風型的高血壓鼠較正常鼠有較大的舒張作用。在易中風型的高血壓鼠,去除內皮細胞顯 著的抑制塞落美引起的舒血管作用,一氧化氮合成脢抑制劑及鳥嘌呤核酸環化脢抑制劑無法 抑制塞落美( 10-5 mole/L )在易中風型的高血壓鼠的血管舒張作用; 然而正常鼠對塞落 美( 10-5 mole/L )引起的舒張作用可被一氧化氮合成脢抑制劑及鳥嘌呤核酸環化脢抑制 劑所防止。 結論:鞘髓磷脂系統可以調節血管張力,易中風型的高血壓鼠對塞落美的舒血管作用改變, 表示高血壓在形成過程中可能改變了鞘髓磷脂的訊息傳遞路徑。 |
英文摘要 | 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 strokeprone 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 (WKY) 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 to 10 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-nitro-L-arginine (L-NNA, 10 mole/L) or methylene blue (10 mole/L). In SHR-SP, removal of the endothelium significantly inhibited ceramide (10 M)-induced relaxation, but L-NNA and methylene blue did not significantly inhibit ceramide-induced relaxation. In contrast, ceramide (10 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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