Enhanced uridine adenosine tetraphosphate-induced contraction in renal artery from type 2 diabetic Goto-Kakizaki rats due to activated cyclooxygenase/thromboxane receptor axis

• Published in: Pflügers Archiv Vol. 466; no. 2; pp. 331 - 342
• Main Authors: Matsumoto, Takayuki, Watanabe, Shun, Kawamura, Ryusuke, Taguchi, Kumiko, Kobayashi, Tsuneo
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.02.2014; Springer Nature B.V
• Subjects: Animals; Biomedical and Life Sciences; Biomedicine; Cell Biology; Cyclooxygenase 1 - metabolism; Cyclooxygenase 2 - metabolism; Cyclooxygenase Inhibitors - pharmacology; Diabetes Mellitus, Type 2 - physiopathology; Dinucleoside Phosphates - pharmacology; Human Physiology; Male; Molecular and Cellular Mechanisms of Disease; Molecular Medicine; Neurosciences; Nitric Oxide Synthase - antagonists & inhibitors; Rats; Rats, Wistar; Receptors; Receptors, Thromboxane - physiology; Renal Artery - drug effects; Vasoconstriction - drug effects; Type 2 diabetes; A; Cyclooxygenase; Up; Thromboxane; Vasoconstriction
• ISSN: 0031-6768; 1432-2013
• DOI: 10.1007/s00424-013-1330-0

The dinucleotide uridine adenosine tetraphosphate (Up 4 A), which has both purine and pyrimidine moieties, was reported as a novel endothelium-derived contracting factor. Recently, growing evidence has suggested that Up 4 A plays an important role in regulation of the cardiovascular function. We previously demonstrated that Up 4 A-induced vasoconstrictions are altered in arteries from DOCA-salt hypertensive rats. We have assessed responses to Up 4 A shown by renal arteries from type 2 diabetic Goto-Kakizaki (GK) rats (42–46 weeks old) and identified the molecular mechanisms involved. Concentration-dependent contractions to Up 4 A were greater in renal arterial rings from the GK than age-matched control Wistar group. In both groups, the inhibition of nitric oxide synthase (with N G -nitro- l -arginine) increased the response to Up 4 A, whereas the inhibition of cyclooxygenase (COX) (with indomethacin) decreased the response. Specific inhibitors of COX-1 (valeroyl salicylate) and COX-2 (NS398), a thromboxane (TX) receptor (TP) antagonist (SQ29548), and P2 receptor antagonist (suramin) also decreased the response to Up 4 A. Protein expressions of COXs in renal arteries were greater in the GK than Wistar group. The production of TXB 2 (a metabolite of TXA 2 ) by Up 4 A did not differ between these groups. Concentration-dependent contractions to U46619, an agonist of the TP receptor, were greater in renal arteries from the GK than Wistar group. The expression of P2X 1 and P2Y 2 receptors did not differ between these groups. These results suggest that enhancement of the Up 4 A-induced contraction in renal arteries from GK rats may be attributable to the increased activation of COXs/TP receptor signaling.