Vascular alpha-1D-adrenoceptors are overexpressed in aorta of the aryl hydrocarbon receptor null mouse: role of increased angiotensin II.
Auton Autacoid Pharmacol
; 28(2-3): 61-7, 2008.
Article
en En
| MEDLINE
| ID: mdl-18598287
1 The hypothesis that alpha(1D)-adrenoceptors may mediate the pro-hypertensive actions of angiotensin II (Ang II) was tested in isolated aorta (alpha(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 alpha(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 alpha(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(-/-)alpha(1D)-adrenoceptors cDNA compared with WT mice; while western blot analysis demonstrated c. 88% increase in alpha(1D)-adrenoceptor protein in AhR(-/-) mice. 7 Captopril therapy decreased alpha(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 alpha(1D)-adrenoceptors are increased, and further suggest that both Ang II and vascular alpha(1D)-adrenoceptors could be related in the onset of hypertension.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Aorta Torácica
/
Angiotensina II
/
Receptores de Hidrocarburo de Aril
/
Receptores Adrenérgicos alfa 1
Límite:
Animals
Idioma:
En
Revista:
Auton Autacoid Pharmacol
Asunto de la revista:
FARMACOLOGIA
/
NEUROLOGIA
Año:
2008
Tipo del documento:
Article
Pais de publicación:
Reino Unido