Modulatory Effect of 2-(4-Hydroxyphenyl)amino-1,4-naphthoquinone on Endothelial Vasodilation in Rat Aorta.
The vascular endothelium plays an essential role in the control of the blood flow. Pharmacological agents like quinone (menadione) at various doses modulate this process in a variety of ways. In this study,Q7, a 2-phenylamino-1,4-naphthoquinone derivative, significantly increased oxidative stress and induced vascular dysfunction at concentrations that were not cytotoxic to endothelial or vascular smooth muscle cells.Q7reduced nitric oxide (NO) levels and endothelial vasodilation to acetylcholine in rat aorta. It also blunted the calcium release from intracellular stores by increasing the phenylephrine-induced vasoconstriction when CaCl2was added to a calcium-free medium but did not affect the influx of calcium from extracellular space.Q7increased the vasoconstriction to BaCl2(10-3M), an inward rectifying K+channels blocker, and blocked the vasodilation to KCl (10-2M) in aortic rings precontracted with BaCl2. This was recovered with sodium nitroprusside (10-8M), a NO donor. In conclusion,Q7induced vasoconstriction was through a modulation of cellular mechanisms involving calcium fluxes through K+channels, and oxidative stress induced endothelium damage. These findings contribute to the characterization of new quinone derivatives with low cytotoxicity able to pharmacologically modulate vasodilation.
Departamento de Ciencias Químicas y Farmacéuticas, Facultad de Ciencias de la Salud, Universidad Arturo Prat, Iquique, Chile.
Javier
J
Palacios
Experimental Physiology Laboratory (EPhyL), Instituto Antofagasta, Universidad de Antofagasta, Antofagasta, Chile.
Fredi
F
Cifuentes
Departamento de Ciencias Químicas y Farmacéuticas, Facultad de Ciencias de la Salud, Universidad Arturo Prat, Iquique, Chile.
Jaime A
JA
Valderrama
Departamento de Ciencias Químicas y Farmacéuticas, Facultad de Ciencias de la Salud, Universidad Arturo Prat, Iquique, Chile.
Julio
J
Benites
Departamento de Ciencias Químicas y Farmacéuticas, Facultad de Ciencias de la Salud, Universidad Arturo Prat, Iquique, Chile.
David
D
Ríos
Departamento de Ciencias Químicas y Farmacéuticas, Facultad de Ciencias de la Salud, Universidad Arturo Prat, Iquique, Chile.
Constanza
C
González
Advanced Center for Chronic Diseases, Faculty of Chemical and Pharmaceutical Sciences, University of Chile, Santiago, Chile.
Mario
0000-0002-5174-6545
M
Chiong
Advanced Center for Chronic Diseases, Faculty of Chemical and Pharmaceutical Sciences, University of Chile, Santiago, Chile.
Benjamín
B
Cartes-Saavedra
Laboratorio de Neurociencias, Centro de Investigaciones Biomédicas, Universidad de los Andes, Monseñor Alvaro del Portillo 12.455, 7550000 Santiago, Chile.
Carlos
0000-0002-6728-1009
C
Lafourcade
Laboratorio de Neurociencias, Centro de Investigaciones Biomédicas, Universidad de los Andes, Monseñor Alvaro del Portillo 12.455, 7550000 Santiago, Chile.
Ursula
U
Wyneken
Facultad de Ciencias Biológicas y Centro UC Investigación en Oncología (CITO), Pontificia Universidad Católica de Chile, Chile.
Pamela
P
González
Facultad de Ciencias Biológicas y Centro UC Investigación en Oncología (CITO), Pontificia Universidad Católica de Chile, Chile.
Gareth I
GI
Owen
Cellular and Molecular Physiology Laboratory (CMPL), Division of Obstetrics and Gynecology, School of Medicine, Faculty of Medicine, Pontificia Universidad Católica de Chile, 8330024 Santiago, Chile.
Fabián
F
Pardo
Cellular and Molecular Physiology Laboratory (CMPL), Division of Obstetrics and Gynecology, School of Medicine, Faculty of Medicine, Pontificia Universidad Católica de Chile, 8330024 Santiago, Chile; Department of Physiology, Faculty of Pharmacy, Universidad de Sevilla, 41012 Seville, Spain; University of Queensland Centre for Clinical Research (UQCCR), Faculty of Medicine and Biomedical Sciences, University of Queensland, Herston, QLD 4029, Australia.
Luis
L
Sobrevia
Departamento de Ciencias Químicas y Farmacéuticas, Facultad de Ciencias de la Salud, Universidad Arturo Prat, Iquique, Chile; Toxicology and Cancer Biology Research Group, Université catholique de Louvain, Brussels, Belgium.
Pedro
0000-0003-0483-2624
P
Buc Calderon
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