1997 Fiscal Year Final Research Report Summary
Causative role of amino acids as neurotransmitters in the ventrolateral medulla for the development of hypertension in the rat
| Project/Area Number |
07670781
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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 |
Circulatory organs internal medicine
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| Research Institution | Osaka University |
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Principal Investigator |
MIKAMI Hiroshi Osaka University, Medical School, Department of Community Health Nursing, Professor, 医学部, 教授 (80173996)
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| Co-Investigator(Kenkyū-buntansha) |
MORIGUCHI Atsushi Osaka University, Medical School, Department of Geriatric Medicine, Assistant Pr, 医学部, 助手 (10273666)
RAKUGI Hiromi Osaka University, Medical School, Department of Geriatric Medicine, Assistant Pr, 医学部, 助手 (20252679)
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| Project Period (FY) |
1995 – 1997
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| Keywords | Angiotensin II / Angiotensin receptor antagonist / Hypertension / Amino acid neurotransmitter / Glutamate / GABA / Glycine / Rostral ventrolateral medulla |
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| Research Abstract |
To investigate the causative role of amino acids as neurotransmitters in the ventrolateral medulla for the development of hypertension in the rat, effects of central amino acid neurons on the antihypertensive action of an angiotensinII type 1 receptor (AT1) antagonist, CV11974, was evaluated. We measured the release of various amino acids in the rostral ventrolateral medulla (RVLM) using the brain microdialysis technique. A microdialysis probe was inserted into the exposed RVLM in male spontaneously hypertensive rats (SHR) anaesthetized with urethane. Mean arterial pressure and the release of amino acids were monitored in response to i.v.CV11974, which decreased pressure and increased the release of inhibitory amino acids, glycine and gamma-aminobutyric acid (GABA) from RVLM.These results suggest that the release of the inhibitory amino acids glycine and GABA in RVLM contributes to the depressor actionof the ATl receptor antagonist in the genetic hypertensive rat model. In another set of experiments where direct application of AII or AT1 antagonist to RVLM was adopted, microinjection of ANG II into RVLM caused a dose-dependent increase in MAP and HR,accompanied by increased release of glutamade in the RVLM.In contrast, microinjection of the AT1 antagonist into RVLM reduced MAP and HR,accompanied by increased release of glycin and GABA.These changes in MAP and HR after administration of ANG II or AT1 antagonist were partially blocked by the use of the corresponding antagonist of each amino acid neurotransmitter. Furthermore, these effects were more prominently seen in SHR than in normotensive rats. These results suggest that the release of amino acid neurotransmitters mediate the cardiovascular effects of the angiotensin system in the RVLM,which may be involved in the generation of hypertension in SHR.
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[Publications] Morishita R,Higaki J,Nakamura Y,Aoki M,Yamada K,Moriguchi A,Rakugi H,Tomita N,Tomita S,Yu H,Nakamura F,Mikami H,Ogihara T: "Effect of an antihypertensive drug on brain angiotensin II levels in renal and spontaneously hypertensice rats." Clinical and Experimental Pharmacology and Physiology. 22 (9). 665-669 (1995)
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「研究成果報告書概要(欧文)」より
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[Publications] Yo Y,Magano M,Moriguchi A,Nakamura F,Kobayashi R,Okuda N,Kamitani A,Nakamura Y,Kamide K,Fujisawa T,Higaki J,Mikami H,Ogihara T: "Predominance of nocturnal sympathetic nervous activity in salt-sensitive normotensive subjects." American Journal of Hypertension. 9 (8). 726-731 (1996)
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「研究成果報告書概要(欧文)」より
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[Publications] Yamada K,Moriguchi A,Morishita R,Higaki J,Aoki M,Nakamura Y,Mikami H,Oshima T,Ninomiya M,Kaneda Y,Ogihara T: "Efficient oligonucleotides delivery using HVJ-liposome method in the central nervous system." American Journal of Physiology. 271 (5). R1212-R1220 (1996)
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