Open AccessImpaired UTP-induced relaxation in the carotid arteries of spontaneously hypertensive rats
Author(s) -
Takayuki Matsumoto,
Mihoka Kojima,
Keisuke Takayanagi,
Tomoki Katome,
Kumiko Taguchi,
Tsuneo Kobayashi
Publication year - 2020
Publication title -
purinergic signalling
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 59
eISSN - 1573-9546
pISSN - 1573-9538
DOI - 10.1007/s11302-020-09721-2
Subject(s) - endocrinology , medicine , spontaneously hypertensive rat , thromboxane , thromboxane a2 , receptor antagonist , uridine triphosphate , vasodilation , prostanoid , phenylephrine , cyclooxygenase , receptor , nitric oxide synthase , nitric oxide , antagonist , chemistry , blood pressure , platelet , enzyme , nucleotide , biochemistry , gene
Uridine 5'-triphosphate (UTP) has an important role as an extracellular signaling molecule that regulates inflammation, angiogenesis, and vascular tone. While chronic hypertension has been shown to promote alterations in arterial vascular tone regulation, carotid artery responses to UTP under hypertensive conditions have remained unclear. The present study investigated carotid artery responses to UTP in spontaneously hypertensive rats (SHR) and control Wistar Kyoto rats (WKY). Accordingly, our results found that although UTP promotes concentration-dependent relaxation in isolated carotid artery segments from both SHR and WKY after pretreatment with phenylephrine, SHR exhibited significantly lower arterial relaxation responses compared with WKY. Moreover, UTP-induced relaxation was substantially reduced by endothelial denudation and by the nitric oxide (NO) synthase inhibitor N G -nitro-L-arginine in both SHR and WKY. The difference in UTP-induced relaxation between both groups was abolished by the selective P2Y 2 receptor antagonist AR-C118925XX and the cyclooxygenase (COX) inhibitor indomethacin but not by the thromboxane-prostanoid receptor antagonist SQ29548. Furthermore, we detected the release of PGE 2 , PGF 2α , and PGI 2 in the carotid arteries of SHR and WKY, both at baseline and in response to UTP. UTP administration also increased TXA 2 levels in WKY but not SHR. Overall, our results suggest that UTP-induced relaxation in carotid arteries is impaired in SHR perhaps due to impaired P2Y 2 receptor signaling, reductions in endothelial NO, and increases in the levels of COX-derived vasoconstrictor prostanoids.