TY - JOUR
T1 - Alteration of vascular responsiveness to uridine adenosine tetraphosphate in aortas isolated from male diabetic otsuka long-evans tokushima fatty rats
T2 - The involvement of prostanoids
AU - Matsumoto, Takayuki
AU - Kobayashi, Shota
AU - Ando, Makoto
AU - Iguchi, Maika
AU - Takayanagi, Keisuke
AU - Kojima, Mihoka
AU - Taguchi, Kumiko
AU - Kobayashi, Tsuneo
N1 - Funding Information:
Acknowledgments: We would like to thank Masanari Ichikawa, Mizuki Iwasaki, Seigo Ohira, Kana Taguchi, Satoshi Noguchi, Kotomi Hatano, and Yoshiko Higashida for the excellent technical assistance. This work was supported in part by JSPS KAKENHI Grant Numbers JP17K08318 (Kumiko Taguchi), and JP15K07975 (Tsuneo Kobayashi), and by Suzuken Memorial Foundation (to Takayuki Matsumoto). The authors would like to thank Enago (www.enago.jp) for the English language review.
Publisher Copyright:
© 2017 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2017/11/9
Y1 - 2017/11/9
N2 - 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 comparedwith those fromage-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.
AB - 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 comparedwith those fromage-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.
KW - Aorta
KW - Contraction
KW - Prostanoid
KW - Relaxation
KW - Type 2 diabetes
KW - Up4A
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UR - http://www.scopus.com/inward/citedby.url?scp=85034032236&partnerID=8YFLogxK
U2 - 10.3390/ijms18112378
DO - 10.3390/ijms18112378
M3 - Article
C2 - 29120387
AN - SCOPUS:85034032236
SN - 1661-6596
VL - 18
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 11
M1 - 2378
ER -
