Vascular α_1D-adrenoceptors are overexpressed in aorta of the aryl hydrocarbon receptor null mouse: Role of increased angiotensin II

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 pEC₅₀. 5 PA₂ 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.