1993 Fiscal Year Final Research Report Summary
Effects of angiotensin II on the release of neurotransmitters from the ventrolateral medulla of the rat
| Project/Area Number |
03670451
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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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 Geriatric Medicine Associate Professor, 医学部, 助教授 (80173996)
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| Co-Investigator(Kenkyū-buntansha) |
NAGANO Masahiro Osaka University, Medical School Department of Geriatric Medicine Assistant Prof, 医学部, 助手 (50228045)
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| Project Period (FY) |
1991 – 1993
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| Keywords | Angiotensin II / Ventrolateral medulla / Baroreflex / Converting enzyme inhibitor / Angiotensin receptor antagonist / Microdialysis / Glutamate / GABA / Glycine |
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| Research Abstract |
We investigated the mechanisms of baroreflex alteration produced by intravenous angiotensin II by monitoring the release of amino acids from the rostral ventrolateral medulla (RVLM) using a brain microdialysis technique. Reflex changes in heart rate were elicited by bolus intravenous injection of phenylephrine before and 120 min after the initiation of administration of a subpressor dose of angiotensin II.The slope of the regression line obtained from changes in mean arterial pressure and heart rate elicited by phenylephrine was used as an index of baroreceptor reflex sensitivity. Angiotensin II attenuated the baroreflex sensitivity which was accompanied with an increase in the release of glutamate and glycine from the LVM at 120 min. Glycine perfusion into this area resulted in an attenuation of baroreflex sensitivity with a magnitude similar to that obtained with infusion of a subpressor dose of ANG II,whereas glutamate perfusion caused a resetting of baroreflex. These results sugges
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t that glycine and glutamate are involved in cardiovascular regulation in the VLM.Furthermore, the augmented releases of these amino acids may account for the underlying mechanisms of angiotensin II-induced attenuation of baroreflex function.
We also test the hypothesis that a central mechanism may play a role in the minimal reflex tachycardia noted in response to peripheral converting enzyme inhibition by comparing the effects of iv ceronapril with a typical vasodilator, nitroglycerin, on the neurotransmitter release in the RVLM with microdialysis method in anesthetized rats. Intravenous ceronapril caused a progressive decrease in glutamate release and attenuated increase in glycine release. Prevention of BP reduction due to ceronapril by concomitant infusion of a subpressor dose of Ang II attenuated the progressive reduction of glutamate release. These results demonstrate that intravenous converting enzyme inhibitor reduces that release of glutamate in the RVLM,which was specifically caused by reducing circulating Ang II resulting in the reduction of BP with minimal effect on the heart rate. Less
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