title: A vasoconstrictor role for cyclooxygenase-1-mediated prostacyclin synthesis in mouse renal arteries.
abstract: This study was to determine whether prostacyclin [prostaglandin I2 (PGI2)] evokes mouse renal vasoconstriction and, if so, the underlying mechanism(s) and how its synthesis via cyclooxygenase-1 (COX-1) influences local vasomotor reaction. Experiments were performed on vessels from C57BL/6 mice and/or those with COX-1 deficiency (COX-1(-/-)). Results showed that in renal arteries PGI2 evoked contraction more potently than in carotid arteries, where COX-1 is suggested to mediate prominent endothelium-dependent contraction. A similar result was observed with the thromboxane-prostanoid (TP) receptor agonist U46619. However, in renal arteries TP receptor antagonism, which inhibited the contraction, did not result in any relaxation in response to PGI2. Moreover, we noted that the endothelial muscarinic receptor agonist ACh evoked an increase in the production of the PGI2 metabolite 6-keto-PGF1α, which was prevented by endothelial denudation or COX-1(-/-). Interestingly, COX-1(-/-) was further found to abolish a force development that was sensitive to TP receptor antagonism and result in enhanced relaxation evoked by ACh following NO synthase inhibition. Also, in renal arteries the COX substrate arachidonic acid evoked a vasoconstrictor response, which was again abolished by COX-1(-/-). Meanwhile, nonselective COX inhibition did not show any effect in vessels from COX-1(-/-) mice. Thus, in mouse renal arteries, high expression of TP receptors together with little functional involvement from the vasodilator PGI2 receptors results in a potent vasoconstrictor effect evoked by PGI2. Also, our data imply that endogenous COX-1-mediated PGI2 synthesis leads to vasoconstrictor activity and this could be an integral part of endothelium-derived mechanisms in regulating local renal vascular function.
authors.affiliation: Cardiovascular Research Center, Shantou Univ. Medical College, 22 Xin-Ling Rd., Shantou, China 515041. zhouyingbi35@gmail.com.
authors.forename: Bin
authors.initials: B
authors.lastname: Liu
authors.forename: Yingzhan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Ningxia
authors.initials: N
authors.lastname: Zhu
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.forename: Wenhong
authors.initials: W
authors.lastname: Luo
authors.forename: Yingbi
authors.initials: Y
authors.lastname: Zhou
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D051545:Cyclooxygenase 1 / Q000235:genetics / Q000502:physiology*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D011464:Epoprostenol / Q000096:biosynthesis*; D005260:Female; D019746:Intramolecular Oxidoreductases / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D044006:Receptors, Epoprostenol / Q000378:metabolism*; D012077:Renal Artery / Q000201:enzymology*; D014661:Vasoconstriction; D014666:Vasomotor System / Q000502:physiology
chemical_list: D044006:Receptors, Epoprostenol; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D003577:Cytochrome P-450 Enzyme System; D011464:Epoprostenol; D051545:Cyclooxygenase 1; D019746:Intramolecular Oxidoreductases; C022461:prostacyclin synthetase
keywords: IP receptors; TP receptors; arachidonic acid; contraction; vasodilation