| Project/Area Number |
14571462
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Anesthesiology/Resuscitation studies
|
|---|
| Research Institution | Wakayama Medical University |
|---|
Principal Investigator |
KAKUTANI Tetsuya Wakayama Medical University, Department of Medicine, Staff, 医学部, 助手 (00264896)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
HATANO Yoshio Wakayama Medical University, Department of Medicine, Professor, 医学部, 教授 (70115913)
|
|---|
| Project Period (FY) |
2002 – 2003
|
| Project Status |
Completed (Fiscal Year 2003)
|
| Budget Amount *help |
¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2003: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2002: ¥1,600,000 (Direct Cost: ¥1,600,000)
|
|---|
| Keywords | hypertensive rat / vascular smooth muscle / angiotensin II receptor / volatile anesthetics / 血管弛緩作用 |
|---|
| Research Abstract |
(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
|
