2002 Fiscal Year Final Research Report Summary
EFFECTS OF GENERAL ANESTHETICS ON INTRACELLULAR CALCIUM CONCENTRATION AND NITRIC OXIDE PRODUCTION OF VASCULAR ENDOTHELIUM
| Project/Area Number |
13671607
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Anesthesiology/Resuscitation studies
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| Research Institution | WAKAYAMA MEDICAL UNIVERSITY |
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Principal Investigator |
OGAWA Koji WAKAYAMA MEDICAL UNIVERSITY, DEPARTMENT OF ANESTHESIOLOGY, ASSISTANT PROFESSOR, 医学部, 講師 (30204077)
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| Co-Investigator(Kenkyū-buntansha) |
HATANO Yoshio WAKAYAMA MEDICAL UNIVERSITY, DEPARTMENT OF ANESTHESIOLOGY, ASSISTANT PROFESSOR, 医学部, 教授 (70115913)
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| Project Period (FY) |
2001 – 2002
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| Keywords | VASCULAR ENDOTHELIUM / INTRACELLULAR CALCIUM CONCENTRATION / ENDOTHELIUM-DEPENDENT RELAXATION / ANESTHETICS |
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| Research Abstract |
An elevation of intracellular Ca^<2+> concentration ([Ca^<2+>]_i) is essential for nitric oxide (NO) production in vascular endothelium. The first goal of this study to elucidate the change in endothelial [Ca^<2+>]_i and NO production induced by receptor-dependent and -independent endothelial activators. The second goal was to investigate the effects of anesthetics on the relationship between [Ca^<2+>]_i and NO production.
Bovine aortic endothelial cells were loaded with fluorescence Ca^<2+> indicator, fura-2/AM (5μM). Fluorescence measurements were performed at excitation wavelength of 340 and 380 nm and an emission wavelength of 510nm. The 340/380 fluorescence ratio (R340/380) was used as an indicator of [Ca^<2+>]_i.
Bradykinin (10nM) elicited a rapid increase in endothelial [Ca^<2+>]_i followed by a gradual decline to a sustained plateau above the resting level. The initial phase was likely caused by intracellular Ca^<2+> release, and the sustained phase was caused by Ca^<2+> influx. In contrast to bradykinin, receptor-independent agonist, A23187 (100nM) induced a monophasic increase in endothelial [Ca^<2+>]_i. Intravenous anesthetics, ketamine (100μM) and etomidate(100μM) attenuated increases in [Ca^<2+>]_i at the peak and sustained phases in response to bradykinin. Neither ketamine nor etomidate altered A23187-induced [Ca^<2+>]_i transient.
Ketamine and etomidate selectively attenuated receptor-mediated endothelium-dependent vasorelaxation by inhibiting of the endothelial [Ca^<2+>]_i transient in response to receptor activation.
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