The role of angiotensin II and the affects of volatile anesthetics on the relaxation of vascular smooth muscle in hypertensive rat

(目的)探讨血管紧张素II受体拮抗剂在全身麻醉期间发生严重低血压的机制。(方法)我们验证了我们的假设，即挥发性麻醉剂会增强自发性高血压大鼠(SHR)血管重构时激动剂诱导的松弛反应。(结果)我们首先检测了Wistar大鼠和SHR分离的血管对挥发性麻醉剂的敏感性，结果两种血管对挥发性麻醉剂的敏感性没有显著差异。因此，我们认为需要可能的细胞内机制来验证假说。之后，我们主要研究麻醉药对血管反应中细胞内现象的相对影响。细胞内钙离子浓度的测定：异氟醚呈剂量依赖性抑制…引起的细胞内钙离子浓度升高Sevoliurane(2MAC)可抑制去甲肾上腺素(10^&lt；-8&gt；M)对血管紧张素II(10^&lt；-7&gt；M~10；-8&gt；M)的增强收缩作用。酶活性的测定(Western Blotting)：蛋白激酶C(PKC)是血管紧张素II诱导的血管收缩过程中细胞内信号转导系统中的关键酶。我们发现，在去甲肾上腺素引起的收缩被血管紧张素II增强的现象中，PKCα是最重要的亚型。此外，我们还研究了Rho激酶在另一种不同于细胞内钙动员的机制中对肌球蛋白轻链磷酸化增强血管平滑肌收缩的作用。结果表明，七氟醚抑制Rho激酶从胞浆到细胞膜的移位，从而抑制血管收缩。这些结果表明，挥发性麻醉剂松弛血管平滑肌的机制不仅影响细胞内钙动员，而且影响细胞内酶信号通路中的钙敏感性。因此，我们需要进一步的研究集中在收缩途径上，以显示麻醉药在高血压患者中的过度松弛。较少

(Purpose) The aim of this study was to investigate the mechanism that severe hypotension occurred during general anesthesia in the patients who received angiotensin II receptor antagonists.(Methods) We examined our hypothesis that volatile anesthetics would enhance the agonist-induced relaxation responses in the spontaneous hypertensive rats (SHR) accompanying with vascular remodeling.(Results) At first we examined the sensitivity to volatile anesthetics in the vessels isolated from Wistar rats and SHR, resulting in no significant differences in both species. Therefore we considered that the possible intracellular mechanism would be needed to demonstrate hypothesis. After then, we mainly studied the relative effects of anesthetics on the intracellular phenomena in vascular responses. We state the summary of this study in the following.The measurement of intracellular calcium concentration : isoflurane dose-dependently inhibited the increase of intracellular calcium concentration induce … More d by the application of angiotensin II. Sevoliurane (2 MAC) inhibited the enhancement of contraction by noradrenalin (10^<-8>M) induced by pretreatment of angiotensin II(10^<-7>M 〜10^<-8>M), but didn't increase intracellular calcium concentration.The measurement of enzymatic activity (Western blotting): Protein kinase C (PKC) is the key enzyme in the intracellular signal transduction system occurring during vascular contraction induced by angiotensin II. We found PKC alpha was the most important subtype in the phenomenon that the contraction by noradrenalin was augmented by the pretreatment of angiotensin II. In addition, we studied the role of Rho kinase which phospholirize myosin light chain to enhance the contraction of vascular smooth muscle in another mechanism different from intracellular calcium mobilization. That results was that sevoflurane inhibited the translocation of Rho kinase from cytoplasm to cellular membrane, resulting in the inhibition of vascular contraction.These findings suggest that volatile anesthetics relax vascular smooth muscle by the mechanism affecting not only the intracellular calcium mobilization but also calcium sensitivity among the intracellular enzymatic signal pathway. Therefore, we need to examine further study which focus on the contraction pathway to demonstrate exaggerated relaxation by anesthetics in hypertensive subjects. Less