title: Vasomotor Reaction to Cyclooxygenase-1-Mediated Prostacyclin Synthesis in Carotid Arteries from Two-Kidney-One-Clip Hypertensive Mice.
abstract: This study tested the hypothesis that in hypertensive arteries cyclooxygenase-1 (COX-1) remains as a major form, mediating prostacyclin (prostaglandin I2; PGI2) synthesis that may evoke a vasoconstrictor response in the presence of functional vasodilator PGI2 (IP) receptors. Two-kidney-one-clip (2K1C) hypertension was induced in wild-type (WT) mice and/or those with COX-1 deficiency (COX-1-/-). Carotid arteries were isolated for analyses 4 weeks after. Results showed that as in normotensive mice, the muscarinic receptor agonist ACh evoked a production of the PGI2 metabolite 6-keto-PGF1α and an endothelium-dependent vasoconstrictor response; both of them were abolished by COX-1 inhibition. At the same time, PGI2, which evokes contraction of hypertensive vessels, caused relaxation after thromboxane-prostanoid (TP) receptor antagonism that abolished the contraction evoked by ACh. Antagonizing IP receptors enhanced the contraction to the COX substrate arachidonic acid (AA). Also, COX-1-/- mice was noted to develop hypertension; however, their increase of blood pressure and/or heart mass was not to a level achieved with WT mice. In addition, we found that either the contraction in response to ACh or that evoked by AA was abolished in COX-1-/- hypertensive mice. These results demonstrate that as in normotensive conditions, COX-1 is a major contributor of PGI2 synthesis in 2K1C hypertensive carotid arteries, which leads to a vasoconstrictor response resulting from opposing dilator and vasoconstrictor activities of IP and TP receptors, respectively. Also, our data suggest that COX-1-/- attenuates the development of 2K1C hypertension in mice, reflecting a net adverse role yielded from all COX-1-mediated activities under the pathological condition.
authors: Cardiovascular Research Center, Shantou University Medical College, Shantou, Guangdong, China.
authors: Bin
authors: B
authors: Liu
authors: Department of Pathology, the Second Affiliated Hospital, Shantou University Medical College, Shantou, Guangdong, China.
authors: Zhenhua
authors: Z
authors: Li
authors: Cardiovascular Research Center, Shantou University Medical College, Shantou, Guangdong, China.
authors: Yingzhan
authors: Y
authors: Zhang
authors: The Central Laboratory, Shantou University Medical College, Shantou, Guangdong, China.
authors: Wenhong
authors: W
authors: Luo
authors: Cardiovascular Research Center, Shantou University Medical College, Shantou, Guangdong, China.
authors: Jiling
authors: J
authors: Zhang
authors: The Central Laboratory, Shantou University Medical College, Shantou, Guangdong, China.
authors: Hui
authors: H
authors: Li
authors: Cardiovascular Research Center, Shantou University Medical College, Shantou, Guangdong, China.
authors: Yingbi
authors: Y
authors: Zhou
mesh_terms: D000818:Animals; D002339:Carotid Arteries / Q000378:metabolism* / Q000473:pathology; D051545:Cyclooxygenase 1 / Q000502:physiology*; D011464:Epoprostenol / Q000378:metabolism*; D006973:Hypertension / Q000209:etiology / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D060888:Real-Time Polymerase Chain Reaction; D017482:Receptors, Thromboxane / Q000378:metabolism; D012077:Renal Artery / Q000601:surgery*; D014661:Vasoconstriction; D014666:Vasomotor System / Q000502:physiology*
chemical_list: D017482:Receptors, Thromboxane; D011464:Epoprostenol; D051545:Cyclooxygenase 1