The Effect of Intravenous Anesthetics on Vascular Function of Arteriovenous Fistula in Normal and Hyperglycemia Rats

目的：我們最近的研究顯示propofol誘發比etomidate更為顯著的血管舒張。但是在某些系統性疾病例如在糖尿病患身上投予propofol或etomidate是會引發更強烈的血液動力改變。本研究在探討propofol及etomidote對糖尿病白鼠的主動脈血管張力之影響，以及其生理機轉。方法：大白鼠接受單一劑量腹腔內注射streptozotocin(65mg/kg)以引發糖尿病。糖尿病誘發六週後，白鼠之主動脈被取下並分離，血管節放置入organ chamber分析其張力變化，有些血管節上的內皮層會被事先刮除。Propofol或etomidate係以續加濃度方式加入Chdmber中（最終濃度為0~300μM）。某些Chamber中會在加入propofol或etomidote前30分鐘投予過氧化物中和劑叫(MnTBAP, 10-5m)或是專一性的KATP channel阻斷劑(glibenclamide, 10-SM)。結果，相較於控制組之白鼠，患有糖尿病的老鼠之主動脈節對propofol及etomidote皆有更顯著之舒張反應。Propofol誘發之血管舒張是與內皮細胞層無關，而此反應可被glienclamide阻斷。相反的，etomidote在糖尿病老鼠主動脈上所引發之舒張反應則是內皮細胞層依賴性的。過氧化物中和劑並不會對這些血管張力變化有影響。結論：在糖尿病老鼠之主動脈中投予propofol或etomidate產生比正常血管更強烈的血管舒張反應。Propofol所誘發之反應是透過誘發血管平滑肌細胞上之KATP chonnel，而etomidote所誘發之反應則是必須經由內皮細胞層媒介。這些有趣的現象值得更進一步的探討。

關鍵字

靜脈麻醉劑；糖尿病鼠；內皮細胞；血管反應

並列摘要

Background. Infusion of propofol often causes significant vasodilation, and followed by drop of blood pressure. However, the exact under1ying mechanisms of this phenomenon remain unc1ear. This study investigated the molecular mechanisms of propofol-induced vasodilation. Objectives & Methods. Changes in isometric tension of pre-contracted aortic segments isolated from control and rats with diabetes mellitus were recorded following cumulative addition of propofol (1 to 600 μM). An ATP-sensitive potassium K(subscript ATP)) channel blocker, glibenclamide (10 μM) was incubated in the organ bath before addition of propofol. Hemodynamic changes after intravenous administration of propofol in the presence or absence of PNU-37885A (a vascular specific K(subscript ATP) channel blocker) were recorded in anesthetized rats. Alterations in intracellular calcium and ATP levels in the vascular smooth muscle cells were measured. Results. Compared with controls or etomidate, propofol induced a concentration dependent vascular relaxation that was independent from the presence of endothelium. The relaxation response was almost completely abolished by K(subscript ATP) channel antagonism. Pre-treatment with PNU-37885A significantly attenuated propofol-induced hypotension. Propofol-induced vasorelaxation was potentiated in the aorta of rats with diabetes mellitus, in which vascular KATP channel was activated due to declined concentrations of intracellular ATP. Conclusions. Development of hypotension following systemic administration of propofol is mainly caused by its direct relaxation effect on the vascular smooth muscle and this response is mediated by the activation of KATP channel.

並列關鍵字

Intravenous anesthetics ； diabetic rats ； endothelium ； vascular response

國際替代計量

The Effect of Intravenous Anesthetics on Vascular Function of Arteriovenous Fistula in Normal and Hyperglycemia Rats

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