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  • Title: Alteration of Vascular Responsiveness to Uridine Adenosine Tetraphosphate in Aortas Isolated from Male Diabetic Otsuka Long-Evans Tokushima Fatty Rats: The Involvement of Prostanoids.
    Author: Matsumoto T, Kobayashi S, Ando M, Iguchi M, Takayanagi K, Kojima M, Taguchi K, Kobayashi T.
    Journal: Int J Mol Sci; 2017 Nov 09; 18(11):. PubMed ID: 29120387.
    Abstract:
    We investigated whether responsiveness to dinucleotide uridine adenosine tetraphosphate (Up₄A) was altered in aortas from type 2 diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats compared with those from age-matched control Long-Evans Tokushima Otsuka (LETO) rats at the chronic stage of disease. In OLETF aortas, we observed the following: (1) Up₄A-induced contractions were lower than those in the LETO aortas under basal conditions, (2) slight relaxation occurred due to Up₄A, but this was not observed in phenylephrine-precontracted LETO aortas, (3) acetylcholine-induced relaxation was reduced (vs. LETO), and (4) prostanoid release (prostaglandin (PG)F2α, thromboxane (Tx)A₂ metabolite, and PGE₂) due to Up₄A was decreased (vs. LETO). Endothelial denudation suppressed Up₄A-induced contractions in the LETO group, but increased the contractions in the OLETF group. Under nitric oxide synthase (NOS) inhibition, Up₄A induced contractions in phenylephrine-precontracted aortas; this effect was greater in the LETO group (vs. the OLETF group). The relaxation response induced by Up₄A was unmasked by cyclooxygenase inhibitors, especially in the LETO group, but this effect was abolished by NOS inhibition. These results suggest that the relaxant component of the Up₄A-mediated response was masked by prostanoids in the LETO aortas and that the LETO and OLETF rats presented different contributions of the endothelium to the response.
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