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PubMed · 9797174

Decrease in glutamic acid decarboxylase level in the hypothalamus of spontaneously hypertensive rats.

E M Horn·C A Shonis·M A Holzwarth·T G Waldrop
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Abstract

BACKGROUND: A reduction in gamma-aminobutyric (GABA)-mediated inhibition of pressor sites in the caudal hypothalamus of spontaneously hypertensive rats compared with that of normotensive Wistar-Kyoto rats has recently been demonstrated. OBJECTIVE: To determine whether the reduction in GABA-mediated inhibition of the caudal hypothalamus of the spontaneously hypertensive rats results from reductions both in the number of GABA-synthesizing neurons and in the amount of the GABA-synthesizing enzyme, glutamic acid decarboxylase messenger RNA (mRNA). DESIGN AND METHODS: A polyclonal antibody (Chemicon) for the 67 kDa isoform of glutamic acid decarboxylase (GAD67) was used to immunocytochemically label GABAergic neurons in the caudal hypothalamus of spontaneously hypertensive and Wistar-Kyoto rats that had been treated beforehand with colchicine. The labeled cells were counted for both strains by a blinded analysis and compared. Caudal hypothalamic tissues from spontaneously hypertensive and Wistar-Kyoto rats were analysed for GAD67 mRNA by Northern blotting. The signal intensities of the radioactive probe specific for GAD67 for the two strains were analyzed by using a phosphorimager and compared. Control areas for the immunocytochemical (zona incerta) and Northern blotting (cortex, midbrain, cerebellum, and brain stem) experiments were used to determine regional differences in expression of GAD67. RESULTS: Both the hypothalamus and cerebellum of spontaneously hypertensive and Wistar-Kyoto rats contained GAD67-immunoreactive neurons; however, there were 42% fewer GAD67 neurons in the caudal hypothalamus of spontaneously hypertensive rats than there were in that of Wistar-Kyoto rats. Furthermore, a 33% reduction in the amount of GAD67 messenger RNA in the caudal hypothalamus of spontaneously hypertensive rats compared with that for Wistar-Kyoto rats was demonstrated. Analysis of the expression of GAD67 in the cortex, midbrain, cerebellum, brain stem, and total brain revealed no difference between spontaneously hypertensive and Wistar-Kyoto rats. CONCLUSIONS: Our findings demonstrate that the spontaneously hypertensive rat has fewer neurons synthesizing GABA and less GAD67 mRNA in the caudal hypothalamus than do Wistar-Kyoto rats. This deficit in the GABAergic system in the caudal hypothalamus, a well-known cardiovascular regulatory site, could contribute to the essential hypertension in this animal model.

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AnimalsDown-RegulationGlutamate DecarboxylaseHypertensionHypothalamusRatsRats, Inbred SHRRats, Inbred WKYJournal ArticleResearch Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, P.H.S.

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E M Horn, C A Shonis, M A Holzwarth, T G Waldrop. 1998. Decrease in glutamic acid decarboxylase level in the hypothalamus of spontaneously hypertensive rats.. https://doi.org/10.1097/00004872-199816050-00010

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