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題 名 | 長期阻斷內生性一氧化氮對血壓的影響:正常鼠與高血壓鼠間的比較=Arterial Pressure Following Chronic Blockade of Endogenous Nitric Oxide in Normotensive and Hypertensive Rats |
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作 者 | 張懷仁; 吳佳諺; 陳幸一; | 書刊名 | 慈濟醫學 |
卷 期 | 11:1 1999.03[民88.03] |
頁 次 | 頁41-50 |
分類號 | 414.41 |
關鍵詞 | 一氧化氮; 一氧化氮生成酶抑制劑; 高血壓; Nitric oxide; NOS inhibitor; Hypertension; |
語 文 | 中文(Chinese) |
中文摘要 | 內生性一氧化氮( NO )在血管平滑肌的舒張作用扮演重要的角色, 在離體主動 脈環、局部血管床及全身之實驗中,急性阻斷 NO 生成均會導致血管變縮及血壓升高。但是 ,NO 在高血壓狀態之角色則尚未完全確立。 有些研究結果指出在高血壓的狀態下,血管內 皮細胞釋放 NO 的能力可能受到損壞; 不過,也有其他的研究者不認為高血壓狀態下的 NO 生成有受影響,甚至有人發覺反而會增加。本實驗室最近研究急性 NO 阻斷對血流動力之作 用, 發現給予 NO 生成�t( NOS )阻斷劑 L-NAME 之後,在正常及高血壓鼠均升高血壓及 周邊血管阻力,而血壓及周邊血管阻力升高之程度,以高血壓鼠比正常鼠為大,顯示高血壓 鼠之 NO 功能反而比正常鼠加強。 本實驗之目的在觀察並比較自發性高血壓鼠( SHR )及 正常血壓鼠( WKY )長期阻斷 NOS 之血壓變化; 並由非選擇性及專一性之 NOS 阻斷以探 討血壓的變化, 是由於 constitutive NOS ( cNOS )或 inducible NOS ( iNOS )受抑 制之結果。利用 SHR ( 6 週齡)及同齡之正常血壓對照組 WKY,每天以胃管灌飲方式一組 給予 NOS 抑制劑 N �� -nitro-L-arginine methyl ester ( L-NAME )( 100 mg/kg/day ),另一組給予 aminoguanidine ( 100 mg/kg/day )持續 6 週以上,以長期阻斷內生性 NO 的生成( L-NAME 為 cNOS 和 iNOS 之抑制劑,aminoguanidine 則選擇性抑制 iNOS ) 。每組大白鼠則每 2-3 天在清醒狀態下測量尾動脈收縮壓( Tail Cuff Pressure,TCP ) 我們發現 L-NAME 會使高血壓鼠( SHR )及正常鼠( WKY )之血壓持續升高,SHR 的升血 壓程度遠較 WKY 為大; 至於 aminoguanidine 不論在 SHR 或 WKY 對於血壓並不造成顯著 影響。實驗結果顯示高血壓鼠的血管內皮細胞依賴的舒張作用不但沒有降低,反而在長期高 血壓狀態產生代償性的 NO 舒張功能增強,對抑制血壓的惡性持續升高有著極重要的保護作 用。而且血壓之變化為抑制 cNOS 之結果,iNOS 阻斷在 SHR 及 WKY 均無顯著之作用。 |
英文摘要 | Endogenous nitric oxide (NO) plays an important role in maintaining relaxation of vascular smooth muscle. In isolated aortic rings, regional vascular beds and whole body, acute NO blockade results in both vasoconstriction and elevated arterial pressure. However, the role of NO in hypertensive state has yet well established. There is conflicting evidence as to whether endothelial function and NO-dependent vasorelaxation are impaired in the hypertensive state. However, our recent studies on arterial hemodynamics found that acute NO synthase (NOS) blockade with L-NAME caused marked increase in arterial pressure (AP) and total peripheral resistance (TPR). The degree of AP and TPR increase was much higher in spontaneously hypertensive rats (SHR) than in normotensive Wistar Kyoto rats (WKY). These results suggest that NO function is enhanced in hypertension. The purpose of the present study was to compare the changes in arterial pressure between spontaneouslyu hypertensive rats and their normotensive counterparts following chronic blockede of NOS. We also investigated the involvement of constitutive NOS (cNOS) and inducible NOS (iNOS) inhibition on blood pressure regulation. In this experiment, SHR (6 weeks of age) and age-matched WKY were divided into experimental and vehicle control groups. The cNOS and iNOS inhibitor N��-nitro-L-arginine methyl ester (L-NAME) (100 mg/kg/day) or the selective iNOS inhibitor aminoguanidine (100 mg/kg/day) was administered by a gastric tube to block the endogenous NO release in conscious WKY and SHR every day for at least 6 weeks. In each group, tail cuff pressure (TCP) was measured in the conscious state every 2-3 days. In both WKY and SHR, we found that L-NAME administration caused a continuous increase in arterial pressure (AP). This AP increase was much higher in SHR than WKY. Aminoguanidine administration did not significantly affect the AP. These results suggest that an enhancement of endothelium-dependent relaxation occurs in SHR and provides a compensatory mechanism to keep the AP at a lower level. NO appears to provide important protection from malignant hypertension. Moreover, the pressor effect of NOS blockade observed in this study results from the inhibition of cNOS. Blockade of iNOS does not have a make significant influence on the AP of either SHR or WKY. |
本系統中英文摘要資訊取自各篇刊載內容。