Cyclooxygenase-dependent vasoconstricting factor(s) in remodelled rat femoral arteries.
OBJECTIVE
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 remodelled arteries following endothelial injury.


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 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 non-specific 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 PGF2alpha receptor antagonist AL-8810. However, the TX synthetase inhibitor OKY-046 had no effect on ACh-induced relaxation in injured arteries.


CONCLUSIONS
In remodelled arteries following photochemical endothelial injury, the vasoconstrictive prostanoids PGH2 and PGF2alpha, but not TXA2, contribute to changes in endothelium-dependent vascular response via COX-1- and 2-dependent pathways.
Hirao
Akiko
A
Department of Clinical Pharmacology and Therapeutics, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu, Shizuoka 431-3192, Japan.
Kondo
Kazunao
K
Takeuchi
Kazuhiko
K
Inui
Naoki
N
Umemura
Kazuo
K
Ohashi
Kyoichi
K
Watanabe
Hiroshi
H
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001685:Biological Factors / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015237:Dinoprost / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D005263:Femoral Artery / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D023421:Models, Animal; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D009578:Nitrobenzenes / Q000494:pharmacology; D044262:Prostaglandin H2 / Q000378:metabolism*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013449:Sulfonamides / Q000494:pharmacology; D014661:Vasoconstriction / Q000502:physiology*; D014664:Vasodilation / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology
D001685:Biological Factors; D016861:Cyclooxygenase Inhibitors; D009578:Nitrobenzenes; D011720:Pyrazoles; C115461:SC 560; D013449:Sulfonamides; D014665:Vasodilator Agents; C067410:endothelium-dependent hyperpolarization factor; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D009569:Nitric Oxide; D044262:Prostaglandin H2; D015237:Dinoprost; D011451:Prostaglandin-Endoperoxide Synthases; D000109:Acetylcholine