Cardiovascular Research Advance Access [Accepted Manuscript] published online on May 2, 2008
Cardiovascular Research, doi:10.1093/cvr/cvn111
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Cyclooxygenase-dependent vasoconstricting factor(s) in remodeled rat femoral arteries
a Departments of Clinical Pharmacology and Therapeutics and Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu, Shizuoka 431-3192, Japan
b Departments of Pharmacology, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu, Shizuoka 431-3192, Japan
c Department of Clinical Pharmacology and Therapeutics, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasama-machi, Yufu, Oita 879-5593, Japan
* Correspondence to: Hiroshi Watanabe, M.D., Ph.D. Department of Clinical Pharmacology and Therapeutics, Hamamatsu University School of Medicine 1-20-1 Handayama, Hamamatsu, 431-3192, Japan Phone: +81 53 435 2385; Fax: +81 53 435 2385 E-mail: hwat{at}hama-med.ac.jp
Aim: Denudation and regeneration of the vascular endothelium are important in the pathogenesis of atherosclerosis. The aim of this study is to clarify the mechanisms of functional alterations in remodeled arteries following endothelial injury.
Methods and Results: Non-mechanical endothelial injury was induced by 540-nm light irradiation of rose Bengal in femoral arteries of Wistar rats. Endothelium-dependent vasodilation was assessed by the response to acetylcholine (ACh) 1, 2 and 4 weeks after the injury. In control arteries ACh-induced relaxation was mainly nitric oxide-dependent at all study time points. In injured arteries, this response was completely restored at 1 week but was more dependent on KCl-sensitive EDHF (endothelium-derived hyperpolarizing factor) production during the first 2 weeks. Cyclooxygenase (COX) isoforms 1 and 2 were detected in the endothelium of injured arteries, and inhibition of prostanoids production with the nonspecific COX inhibitor indomethacin substantially enhanced the ACh-induced vasorelaxation response in injured arteries, but did not affect control arteries. Similar effects were observed with the COX-1 inhibitor SC-560, the COX-2 inhibitor NS-398, the thromboxane (TX) A2/prostaglandin (PG) H2 receptor antagonist SQ29548 and the PGF2
receptor antagonist AL-8810. However, the thromboxane synthetase inhibitor OKY-046 had no effect on ACh-induced relaxation in injured arteries.
Conclusions: In remodeled arteries following photochemical endothelial injury, the vasoconstrictive prostanoids PGH2 and PGF2, but not TXA2, contribute to changes in endothelium-dependent vascular response via COX-1- and 2-dependent pathways.
Time for primary review: 25 days
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