1987 Fiscal Year Final Research Report Summary
Studies on the role of medullary alpha-2 adrenoceptors in experimental hypertension
| Project/Area Number |
61571098
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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 |
応用薬理学・医療系薬学
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| Research Institution | School of Pharmaceutical Sciences, University of Shizuoka (1987)
Shizuoka College of Pharmacy (1986) |
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Principal Investigator |
YAMADA SHIZUO School of Pharmaceutical Sciences, University of Shizuoka, 薬学部, 助手 (80106434)
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| Project Period (FY) |
1986 – 1987
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| Keywords | Spontaneously hypertensive rats(SHR, SHRSP) / medulla oblongata / radioreceptor assay / _2-adrenoceptors / clonidine / カテコールアミン作働性神経活性 |
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| Research Abstract |
To study the role of medullary <alpha>_2-adrenoceptors in hypertension, we have measured <alpha>_1 and <alpha>_2-adrenoceptors in the medulla oblongata of normotensive Wistar Kyoto rats(WKY), spontaneously hypertensive rats(SHR) and stroke-prone SHR(SHRSP), by using radioligand(<alpha>_1: ^3H-prazosin, <alpha>_2: ^3H-clonidine) bindin technique. Compared to age-matched WKY, there was a significant decrease in the number of <alpha>_2 but not <alpha>_1-adrenoceptors without a change in the affinity in the medulla oblongata of SHR and SHRSP at the established stage(16-24 week old) of hypertension. The decrease was prominent in the dorsomedial and ventrolateral regions of hypertensive medulla oblongata. The decreased density of medullary <alpha>_2-adrenoceptors was also observed in young(4-5 week old) SHRSP. The dorsomedial and ventrolateral regions of the SHRSP medulla oblongata showed significantly lower levels of norepinephrine. Chronic treatment(3 weeks) of young WKY an dSHRSP with clonidine showed a specific decrease in the medullary (dorsomedial and ventrolateral regions) <alpha>_2-adrenoceptors.
Because <alph>_2-adrenoceptors in dorsomedial and ventrolateral regions of medulla oblongata are significantly involved in the inhibitory control of cardiovascular function, loss of medullary <alph>_2-adrenoceptors in SHR and SHRSP may cause the dysfunction of " normal depressor mechanism ", which consequently leads to a rise in the blood pressure. Thus, the present study suggests an implicated role for medullary <alph>_2-adrenoceptors in the development of spontaneous hypertension.
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