title: Vascular alpha-1D-adrenoceptors are overexpressed in aorta of the aryl hydrocarbon receptor null mouse: role of increased angiotensin II.
abstract: 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.
authors.affiliation: Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla, México.
authors.forename: R
authors.initials: R
authors.lastname: Villalobos-Molina
authors.forename: F G
authors.initials: FG
authors.lastname: Vázquez-Cuevas
authors.forename: J J
authors.initials: JJ
authors.lastname: López-Guerrero
authors.forename: M C
authors.initials: MC
authors.lastname: Figueroa-García
authors.forename: I A
authors.initials: IA
authors.lastname: Gallardo-Ortiz
authors.forename: M
authors.initials: M
authors.lastname: Ibarra
authors.forename: M
authors.initials: M
authors.lastname: Rodríguez-Sosa
authors.forename: F J
authors.initials: FJ
authors.lastname: Gonzalez
authors.forename: G
authors.initials: G
authors.lastname: Elizondo
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects; D015153:Blotting, Western; D002216:Captopril / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009638:Norepinephrine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D018340:Receptors, Adrenergic, alpha-1 / Q000235:genetics / Q000378:metabolism*; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014661:Vasoconstriction / Q000187:drug effects
chemical_list: C547720:Adra1d protein, mouse; D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D010879:Piperazines; D018340:Receptors, Adrenergic, alpha-1; D018336:Receptors, Aryl Hydrocarbon; D000804:Angiotensin II; D010656:Phenylephrine; D002216:Captopril; C053428:BMY 7378; D009638:Norepinephrine