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.
Highlights
Diabetes is one of the most common diseases occurring worldwide, yet it remains difficult to manage this disease and its associated complications [1]
Numerous vasoactive factors are released from the endothelium via various stimuli, and vascular tone is regulated through the release of various factors, including endotheliumderived relaxing factors (EDRFs) such as nitric oxide (NO), prostacyclin (PGI2), and endothelium-derived hyperpolarizing factor, as well as endothelium-derived contracting factors (EDCFs) such as endothelin-1 and vasoconstrictor prostanoids [9,10,11,12,13,14,15]
Our results indicated that the endothelium and COX-derived prostanoids play roles in the Up4A-mediated responses in the aorta, and the contributions of the endothelium and COX-derived prostanoids to these responses differ over the long-term course of diabetes
Summary
Diabetes is one of the most common diseases occurring worldwide, yet it remains difficult to manage this disease and its associated complications [1]. Zhou et al [37] reported that Up4A-induced contraction in mouse aortas was suppressed by COX inhibition These results suggest that in some conditions there occurs cross-talk between Up4A and vasoconstrictor prostanoids in arteries, and these are important regulators of vascular function [8,11,12,14]; little is known regarding the relationship between COX-derived prostanoids and Up4A-induced responses in large arteries under diabetic conditions, especially long-term type 2 diabetes. Using molecular and pharmacological approaches, we investigated the relationships between Up4A-mediated responses and endothelium-derived factors in the diabetic aorta
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
