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Evidence that α1D‐Adrenoceptors Are Overexpressed in Aorta of the Aryl Hydrocarbon Receptor Null Mouse
Author(s) -
GALLARDOORTIZ ITZELL A.,
IBARRA MAXIMILIANO,
VILLALOBOSMOLINA RAFAEL
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.lb19
Subject(s) - captopril , endocrinology , medicine , aryl hydrocarbon receptor , phenylephrine , chemistry , western blot , losartan , receptor , adrenergic receptor , contraction (grammar) , angiotensin ii , blood pressure , antagonist , biology , biochemistry , gene , transcription factor
The hypothesis that α 1D ‐adrenoceptors may mediate the pro‐hypertensive actions of Ang II was tested in isolated aorta (α 1D ‐adrenoceptor bearing tissue) of the aryl hydrocarbon receptor null mouse increased levels of Ang II, cardiac (AhR −/− ), which shows hypertrophy and hypertension. The effect of captopril (Angiotensin Converting Enzyme inhibitor) in both blood pressure and aortic α 1D ‐adrenoceptor expression and function in mice was determined. Basal blood pressure was higher in AhR −/− mice, while captopril therapy decreased it to WT values. Aortas of adult WT and AhR −/− mice were stimulated by phenylephrine or norepinephrine to induce contraction; the maximal effect was higher in AhR −/− mice, without a significant change in pEC 50 . The selective α 1D ‐adrenoceptor antagonist BMY 7378 (8‐[2‐[4‐(2‐methoxyphenyl)‐1‐piperazynil]ethyl]‐8‐azaspiro [4.5]decane‐7,9‐dione) showed pA 2 values of 9.19 and 8.94 for WT and AhR −/− , respectively; while Schild slopes were not different from 1. PCR experiments showed ≈ 77% increase in AhR −/− α 1D ‐adrenoceptors cDNA as compared to WT mice; while western blot showed ≈ 88% increase in α 1D ‐adrenoceptor protein in AhR −/− mice. Captopril therapy decreased α 1D ‐adrenoceptor‐induced contraction and protein in AhR −/− mice to WT levels. Authors thank CONACYT (grant 47481), PAPIIT (grants IN203205 and IN218406‐3) and Fundación Miguel Alemán for support. IAGO is a doctoral student.