Effect of clofibrate on vascular reactivity in a model of high blood pressure secondary to aortic coarctation
Por:
Cervantes-Pérez L.G., Ibarra-Lara M.D.L.L., Rubio M.E., Escalante B., Pérez-Severiano F., Soria-Castro E., Ramírez-Ortega M.D.C., Sánchez-Mendoza M.A.
Publicada:
1 ene 2010
Categoría:
Pharmacology
Resumen:
The aims of this study were to identify the effect of clofibrate administration in the development of high blood pressure secondary to aortic coarctation (AoCo) and to assess its effect on vascular reactivity. Three experimental groups of rats were used: sham-operated, aortic coarctated vehicle-treated (AoCo-V), and aortic coarctated clofibrate-treated (AoCo-C100). The rats were treated for seven days. Blood pressure was measured, and the vascular response to angiotensin II (AngII), norepinephrine (NE), and acetylcholine (ACh) were evaluated in aortic rings. The activity and expression of endothelial nitric oxide synthase (eNOS) was also evaluated. The major findings of this study include the following: AoCo induced a rise in blood pressure, and this effect was attenuated by clofibrate. The vascular response to AngII was higher in aortic rings from the AoCo-V group compared to the Sham-V or AoCo-C100 groups. ACh-elicited vasorelaxation was lower in the arteries of AoCo-V rats than Sham-V or AoCo-C100, while it was comparable between the Sham-V and AoCo-C100 groups. In every case, vasorelaxation was dependent on NO. However, the ACh-induced release of NO as well as NOS activity and expression were reduced in the arteries of AoCo-V rats. Clofibrate maintained normal NOS activity and increased eNOS expression. In conclusion, clofibrate administration attenuated the AoCo-induced rise in blood pressure by a mechanism that involves the participation of the NO system at both the NO synthesis and the eNOS protein expression levels. These events improved endothelial function, preserved normal vascular responses to both vasorelaxants and vasoconstrictors, and led to better blood pressure control. Copyright © 2010 by Institute of Pharmacology Polish Academy of Sciences.
Filiaciones:
Cervantes-Pérez L.G.:
Department of Pharmacology, National Institute of Cardiology Ignacio Chávez, Tlalpan, México DF, CP 14080, Mexico
Department of Molecular Biomedicine, Research and Advanced Studies Center of the National Polytechnic, Institute of Mexico, V. Conocimiento 201, km 9.5 Autopista Nueva al Aeropuerto, Apodaca NL, México CP 66600, Mexico
Ibarra-Lara M.D.L.L.:
Department of Pharmacology, National Institute of Cardiology Ignacio Chávez, Tlalpan, México DF, CP 14080, Mexico
Rubio M.E.:
Department of Physiology, National Institute of Cardiology Ignacio Chávez, Tlalpan, México DF, CP 14080, Mexico
Escalante B.:
Department of Molecular Biomedicine, Research and Advanced Studies Center of the National Polytechnic, Institute of Mexico, V. Conocimiento 201, km 9.5 Autopista Nueva al Aeropuerto, Apodaca NL, México CP 66600, Mexico
Pérez-Severiano F.:
Department of Neurochemistry, National Institute of Neurology and Neurosurgery Manuel Velasco Suárez, Av. Insurgentes Sur No. 3877 Col. La Fama, Tlalpan México DF, CP 14269, Mexico
Soria-Castro E.:
Department of Pathology, National Institute of Cardiology Ignacio Chávez, Juan Badiano No. 1 Col. Sección XVI, Tlalpan, México DF, CP 14080, Mexico
Ramírez-Ortega M.D.C.:
Department of Pharmacology, National Institute of Cardiology Ignacio Chávez, Tlalpan, México DF, CP 14080, Mexico
Sánchez-Mendoza M.A.:
Department of Pharmacology, National Institute of Cardiology Ignacio Chávez, Tlalpan, México DF, CP 14080, Mexico
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