Open AccessVascular α 1D ‐adrenoceptors are overexpressed in aorta of the aryl hydrocarbon receptor null mouse: role of increased angiotensin II
Author(s) -
VillalobosMolina R.,
VázquezCuevas F. G.,
LópezGuerrero J. J.,
FigueroaGarcía M. C.,
GallardoOrtiz I. A.,
Ibarra M.,
RodríguezSosa M.,
Gonzalez F. J.,
Elizondo G.
Publication year - 2008
Publication title -
autonomic and autacoid pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.44
H-Index - 21
eISSN - 1474-8673
pISSN - 1474-8665
DOI - 10.1111/j.1474-8673.2008.00418.x
Subject(s) - medicine , endocrinology , captopril , aryl hydrocarbon receptor , phenylephrine , angiotensin ii , chemistry , losartan , western blot , angiotensin converting enzyme , receptor , blood pressure , adrenergic receptor , biology , biochemistry , gene , transcription factor
Summary 1 The hypothesis that α 1D ‐adrenoceptors may mediate the pro‐hypertensive actions of angiotensin II (Ang II) was tested in isolated aorta (α 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 α 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 pEC 50 . 5 PA 2 values for the selective α 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 −/− α 1D ‐adrenoceptors cDNA compared with WT mice; while western blot analysis demonstrated c. 88% increase in α 1D ‐adrenoceptor protein in AhR −/− mice. 7 Captopril therapy decreased α 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 α 1D ‐adrenoceptors are increased, and further suggest that both Ang II and vascular α 1D ‐adrenoceptors could be related in the onset of hypertension.