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受体拮抗剂在全麻期间发生严重低血压的机制。（方法）在伴有血管重构的自发性高血压大鼠（SHR）模型上，我们验证了挥发性麻醉药增强激动剂引起的舒张反应的假说。（结果）Wistar大鼠和SHR血管对挥发性麻醉药的敏感性无明显差异。因此，我们认为可能的细胞内机制将需要证明假设。在此基础上，我们重点研究了麻醉药对血管反应中细胞内现象的影响。细胞内钙离子浓度的测定：异氟醚剂量依赖性地抑制了诱导的心肌细胞内钙离子浓度的升高 ...更多信息 d应用血管紧张素II。西佛柳烷（2 MAC）抑制血管<-8>紧张素Ⅱ（10 μ M × 10 μ M）预处理引起的去甲肾上腺素（10 μ M）<-7><-8>对血管收缩的增强作用，但不增加细胞内钙离子浓度.酶活性测定（Western blotting）：蛋白激酶C（PKC）是血管紧张素Ⅱ引起血管收缩过程中细胞内信号转导系统的关键酶。我们发现PKC α是血管紧张素II预处理增强去甲肾上腺素收缩的现象中最重要的亚型。此外，我们还研究了Rho激酶磷酸化肌球蛋白轻链以增强血管平滑肌收缩的另一种不同于细胞内钙动员的机制。结果表明，七氟醚可抑制Rho激酶从细胞质向细胞膜的转位，从而抑制血管收缩，提示挥发性麻醉药通过影响细胞内钙动员和细胞内酶信号通路中的钙敏感性来舒张血管平滑肌。因此，我们需要进一步的研究，重点是收缩途径，以证明过度放松麻醉剂在高血压受试者。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