Vascular α1D-adrenoceptors are overexpressed in aorta of the aryl hydrocarbon receptor null mouse: role of increased angiotensin II
1 The hypothesis that α1D-adrenoceptors may mediate the pro-hypertensive actions of angiotensin II (Ang II) was tested in isolated aorta (α1D-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 α1D-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 α1D-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−/−α1D-adrenoceptors cDNA compared with WT mice; while western blot analysis demonstrated c. 88% increase in α1D-adrenoceptor protein in AhR−/− mice.
7 Captopril therapy decreased α1D-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 α1D-adrenoceptors are increased, and further suggest that both Ang II and vascular α1D-adrenoceptors could be related in the onset of hypertension.
Document Type: Research Article
Affiliations: 1: Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla, México 2: Departamento de Farmacobiología, Sede Sur, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, México D.F., México 3: Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA 4: Sección Externa de Toxicología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, México D.F., México
Publication date: April 1, 2008