Title: Differential expression of α<sub>2D</sub>-adrenoceptor and eNOS in aortas from early and later stages of diabetes in Goto-Kakizaki rats
Abstract: The aim of the present study was to compare vascular dysfunction between the early (12 wk old) and later (36 wk old) stages of spontaneous diabetes in Goto-Kakizaki (GK) rats. We also evaluated the aortic expression of the α 2D -adrenoceptor and endothelial nitric oxide synthase (eNOS). Vascular reactivity was assessed in thoracic aortas from age-matched control rats and 12- and 36-wk GK rats. Using RT-PCR and immunoblots, we also examined the changes in expression of the α 2D- adrenoceptor and eNOS. In aortas from GK rats (vs. those from age-matched control rats): 1) the relaxation response to ACh was enhanced at 12 wk but decreased at 36 wk; 2) the relaxation response to sodium nitroprusside was decreased at both 12 and 36 wk, 3) norepinephrine (NE)-induced contractility was decreased at 12 wk but not at 36 wk, 4) the expressions of α 1B - and α 1D -adrenoceptors were unaffected, whereas those of α 2D -adrenoceptor and eNOS mRNAs were increased at both 12 and 36 wk; and 5) NE- and ACh-stimulated NO x (nitrite and nitrate) levels were increased at 12 wk, although at 36 wk ACh-stimulated NO x was lower, whereas NE-stimulated NO x showed no change. These results clearly demonstrate that enhanced ACh-induced relaxation and impaired NE-induced contraction, due to NO overproduction via eNOS and increased α 2D -adrenoceptor expression, occur in early-stage GK rats and that the impaired ACh-induced relaxation in later-stage GK rats is due to reductions in both NO production and NO responsiveness (but not in eNOS expression).
Publication Year: 2004
Publication Date: 2004-07-01
Language: en
Type: article
Indexed In: ['crossref', 'pubmed']
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Cited By Count: 57
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