Vascular a1D-adrenoceptors are overexpressed in aorta of the aryl hydrocarbon receptor null mouse: Role of increased angiotensin II
Por:
Villalobos-Molina R., Vázquez-Cuevas F.G., López-Guerrero J.J., Figueroa-García M.C., Gallardo-Ortiz I.A., Ibarra M., Rodríguez-Sosa M., Gonzalez F.J., Elizondo G.
Publicada:
1 ene 2008
Categoría:
Pharmacology
Resumen:
1 The hypothesis that ?1D-adrenoceptors may mediate the pro-hypertensive actions of angiotensin II (Ang II) was tested in isolated aorta (?1D-adrenoceptor bearing tissue) of the aryl hydrocarbon receptor null mouse (AhR-/-), which shows increased levels of Ang II, cardiac hypertrophy and hypertension. 2 The effect of captopril (an angiotensin converting enzyme inhibitor) on both blood pressure and aortic ?1D-adrenoceptor expression and function in mice were determined. 3 Basal blood pressure was higher in AhR-/- mice, while captopril therapy decreased it to wild-type (WT) values. 4 Aortas of adult WT and AhR-/- mice were stimulated by phenylephrine or noradrenaline to induce contraction; the maximal effect was higher in AhR-/- mice, without a significant change in pEC50. 5 PA2 values for the selective ?1D-adrenoceptor antagonist BMY 7378 (8-[2-[4-(2-methoxyphenyl)-1-piperazynil]ethyl]-8-azaspiro [4.5]decane-7,9- dione) were 9.19 and 8.94 for WT and AhR-/-, respectively; while Schild slopes were not different from 1. 6 PCR experiments showed c. 77% increase in AhR-/- ?1D-adrenoceptors cDNA compared with WT mice; while western blot analysis demonstrated c. 88% increase in ?1D-adrenoceptor protein in AhR-/- mice. 7 Captopril therapy decreased ?1D-adrenoceptor-induced contraction and protein in AhR-/- mice to WT levels. 8 These data support the hypothesis that under conditions where Ang II is elevated, vascular ?1D-adrenoceptors are increased, and further suggest that both Ang II and vascular ?1D-adrenoceptors could be related in the onset of hypertension. © 2008 The Authors.
Filiaciones:
Villalobos-Molina R.:
Unidad de biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla, Mexico
Vázquez-Cuevas F.G.:
Unidad de biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla, Mexico
López-Guerrero J.J.:
Departamento de Farmacobiología, Sede Sur, Centro de Investigación Y de Estudios Avanzados, Instituto Politécnico Nacional, México D.F., Mexico
Figueroa-García M.C.:
Unidad de biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla, Mexico
Gallardo-Ortiz I.A.:
Unidad de biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla, Mexico
Ibarra M.:
Unidad de biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla, Mexico
Rodríguez-Sosa M.:
Unidad de biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla, Mexico
Gonzalez F.J.:
Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States
Elizondo G.:
Sección Externa de Toxicología, Centro de Investigación Y de Estudios Avanzados, Instituto Politécnico Nacional, México D.F., Mexico
All Open Access; Green
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