| Project/Area Number |
11470319
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 | TOYAMA MEDICAL AND PHARMACEUTICAL UNIVERSITY |
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Principal Investigator |
YAMAZAKI Mitsuaki Toyama Medical and Pharmaceutical University Faculty of Medicine Professor, 医学部, 教授 (70158145)
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| Co-Investigator(Kenkyū-buntansha) |
NAGAKAWA Tamotsu Toyama Medical and Pharmaceutical University Faculty of Medicine Instructor, 医学部, 助手 (90237503)
SHIBUYA Nobuko Toyama Medical and Pharmaceutical University University Hospital Assistant Professor, 附属病院, 講師 (40178926)
HATAKEYAMA Noboru Toyama Medical and Pharmaceutical University University Hospital Assistant Professor, 附属病院, 講師 (70251907)
伊藤 祐輔 富山医科薬科大学, 医学部, 教授 (70018307)
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| Project Period (FY) |
1999 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥11,500,000 (Direct Cost: ¥11,500,000)
Fiscal Year 2002: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2001: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2000: ¥4,600,000 (Direct Cost: ¥4,600,000)
Fiscal Year 1999: ¥4,300,000 (Direct Cost: ¥4,300,000)
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| Keywords | vascular smooth muscle / transmembrane potential / isoflurane / sevoflurane / propofol / potassium channel / EDHF / hypertension / cAMP / SQ22536 / Rp-cAMPS / L-NAME / NO-cGMP系 / K^+チャネル / EDHA / アセチルコリン / WKYラット / SHRラット |
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| Research Abstract |
We indirectly assessed the in vivo effect of anesthetics on vascular smooth muscle (VSM) tone in SD rats by measurement of in situ responses of VSM transmembrane potential in small mesenteric arteries and veins. Measurements were made before, during, and after anesthetic or inhibitor infusions into vessels.
1. Inhaled anesthetics attenuate both sympathetic neural and nonneural regulation of VSM transmembrane potentials and tone.
2. In the neurogenic SH rat model of human hypertension, a primary mechanism underlying elevated isoflurane-induced VSM heperpolarization in both resistance- and capacitance-regulating blood vessels is a central neural inhibition of excitatory sympathetic input. Peripheral neural and nonneurally mediated hyperpolarization by isoflurane is similar in SH and WKY rat VSM.
3. Measurements were taken in the presence and absence of selective inhibitors of eaeh of four types of potassium channels. Propofol-mediated hyperpolarization of VSM can be attributed in part to an opening of K_Ca and K_ATP but not K_V and K_IR.
4. Ach hyperpolarized arterial, but not venous VSM. Ach-induced (EDHF) hyperpolarization was eliminated by propofol. These results suggest that propofol attenuates both sympathetic neural and nonneural regulation of VSM tone. They also suggest that propofol and Ach may act competitively in the second messenger cascade regulating VSMK^+ channel activity in mesenteric resistance arteries.
5. Propofol-mediated hyperpolarization of VSM can be attributed in part to NO-cGMP pathway but not PGI_2-cAMP pathway.
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