title: Involvement of cyclo-oxygenase-1-mediated prostacyclin synthesis in the vasoconstrictor activity evoked by ACh in mouse arteries.
abstract: This study was to determine whether the endothelium of mouse major arteries produces prostacyclin (PGI(2)) and, if so, to determine how PGI(2) affects vasomotor reactivity and whether cyclo-oxygenase-1 (COX-1) contributes to PGI(2) synthesis. Abdominal aortas, carotid and femoral arteries were isolated from wild-type mice and/or those with COX-1 or -2 deficiency (COX-1(-/-); COX-2(-/-)) for biochemical and/or functional analyses. The PGI(2) metabolite 6-keto-PGF(1α) was analysed with high-performance liquid chromatography-mass spectroscopy, while vasoreactivity was determined with isometric force measurement. Results showed that in the abdominal aorta, ACh evoked endothelium-dependent production of 6-keto-PGF(1α), which was abolished by COX-1(-/-), but not by COX-2(-/-). Interestingly, COX-1(-/-) enhanced the dilatation in response to ACh, while PGI(2), which evoked relaxation of the mesenteric artery, caused contraction that was abolished by antagonizing thromboxane prostanoid (TP) receptors in the abdominal aorta. However, the TP receptor agonist U46619 evoked similar contractions in the abdominal aorta and mesenteric artery. Also, antagonizing TP receptors enhanced the relaxation in response to PGI(2) in mesenteric arteries. Real-time PCR showed that the PGI(2) (IP) receptor mRNA level was lower in the abdominal aorta than in mesenteric arteries. In addition, COX-1(-/-) not only abolished the contraction in response to ACh following NO inhibition in abdominal aorta, but also those in the carotid and femoral arteries. These results demonstrate an explicit role for endothelial COX-1 in PGI(2) synthesis and suggest that in given mouse arteries, PGI(2) mediates not dilatation but rather vasoconstrictor activity, possibly due to a low expression or functional presence of IP receptors, which enables PGI(2) to act mainly on TP receptors.
authors.affiliation: Cardiovascular Research Center, Shantou University College of Medicine, 22 Xin-Ling Road, Shantou, China 515041.
authors.forename: Bin
authors.initials: B
authors.lastname: Liu
authors.forename: Wenhong
authors.initials: W
authors.lastname: Luo
authors.forename: Yingzhan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.forename: Ningxia
authors.initials: N
authors.lastname: Zhu
authors.forename: Dongyang
authors.initials: D
authors.lastname: Huang
authors.forename: Yingbi
authors.initials: Y
authors.lastname: Zhou
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D051545:Cyclooxygenase 1 / Q000235:genetics / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D011464:Epoprostenol / Q000096:biosynthesis* / Q000378:metabolism; D019746:Intramolecular Oxidoreductases / Q000235:genetics / Q000378:metabolism; D007537:Isometric Contraction / Q000187:drug effects / Q000502:physiology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics; D017482:Receptors, Thromboxane / Q000378:metabolism; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects* / Q000235:genetics / Q000502:physiology
chemical_list: D008565:Membrane Proteins; D012333:RNA, Messenger; D017482:Receptors, Thromboxane; D014662:Vasoconstrictor Agents; D009569:Nitric Oxide; D015121:6-Ketoprostaglandin F1 alpha; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D003577:Cytochrome P-450 Enzyme System; D011464:Epoprostenol; D019001:Nitric Oxide Synthase; C077623:Ptgs2 protein, mouse; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496512:Ptgs1 protein, mouse; D019746:Intramolecular Oxidoreductases; C022461:prostacyclin synthetase; D000109:Acetylcholine