Attenuated Aortic Vasodilation and Sympathetic Prejunctional Facilitation in Epinephrine-Deficient Mice: Selective Impairment of beta(2)-Adrenoceptor Responses

• Type: Article in International Scientific Journal
• Date: 2014

Authors

Monica Moreira Rodrigues (Author) Other; Ana L Graca (Author) Other; Marlene Ferreira (Author) Other; Joana Afonso (Author) Other; Paula Serrao (Author) Other; Manuela Morato (Author) FFUP; Fatima Ferreirinha (Author) Other; Paulo Correia de Sá (Author) ICBAS; Steven N Ebert (Author) Other; Daniel Moura (Author) Other; Mónica Moreira-Rodrigues (Author) ICBAS

Journal

Title: Journal of Pharmacology and Experimental Therapeutics

Vol. 351

Pages: 243-249

ISSN: 0022-3565

Publisher: American Society for Pharmacology and Experimental Therapeutics

Indexing

ISI Web of Knowledge - 15 Citations

Scopus - 15 Citations

Scientific classification

FOS: Medical and Health sciences > Basic medicine

Other information

Authenticus ID: P-009-TAH

DOI: 10.1124/jpet.114.217281

Abstract (EN): It has been suggested that there is a link between epinephrine synthesis and the development of beta(2)-adrenoceptor-mediated effects, but it remains to be determined whether this development is triggered by epinephrine. The aim of this study was to characterize beta-adrenoceptor-mediated relaxation and facilitation of norepinephrine release in the aorta of phenylethanolamine-N-methyltransferase-knockout (Pnmt-KO) mice. Catecholamines were quantified by reverse-phase high-performance liquid chromatography-electrochemical detection. Aortic rings were mounted in a myograph to determine concentration-response curves to selective beta(1)- or beta(2)-adrenoceptor agonists in the absence or presence of selective beta(1)- or beta(2)-adrenoceptor antagonists. Aortic rings were also preincubated with [H-3] norepinephrine to measure tritium overflow elicited by electrical stimulation in the presence of increasing concentrations of nonselective beta- or selective beta(2)-adrenoceptor agonists. beta(2)-Adrenoceptor protein density was evaluated by Western blotting and beta(2)-adrenoceptor localization by immunohistochemistry. Epinephrine is absent in Pnmt-KO mice. The potency and the maximal effect of the beta(2)-adrenoceptor agonist terbutaline were lower in Pnmt-KO than in wild-type (WT) mice. The selective beta(2)-adrenoceptor antagonist ICI 118,551 [(+/-)-erythro-(S*, S*)-1-[2,3-(dihydro-7-methyl-1H-inden-4-yl)oxy]-3-[(1-methylethyl) amino]-2-butanol hydrochloride] antagonized the relaxation caused by terbutaline in WT but not in Pnmt-KO mice. Isoproterenol and terbutaline induced concentration-dependent increases in tritium overflow in WT mice only. beta(2)-Adrenoceptor protein density was decreased in membrane aorta homogenates of Pnmt-KO mice, and this finding was supported by immunofluorescence confocal microscopy. In conclusion, epinephrine is crucial for beta(2)-adrenoceptor-mediated vasodilation and facilitation of norepinephrine release. In the absence of epinephrine, beta(2)-adrenoceptor protein density was decreased in aorta cell membranes, thus potentially hindering its functional activity.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 7