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The impact of alpha1-adrenoceptors up-regulation accompanied by the impairment of beta-adrenergic vasodilatation in hypertension

AuthorsOliver, Eduardo; Martí, Daniel; Montó, Fermí; Flacco, Nicla; Moreno, Lucrecia; Barettino, Domingo ; Ivorra, M. Dolores; D'Ocón, Pilar
Issue DateMar-2009
PublisherAmerican Society for Pharmacology and Experimental Therapeutics
CitationJournal of Pharmacology and Experimental Therapeutics 328(3):982-90 (2009)
AbstractIn human and animal hypertension models, increased activity of G-protein-coupled receptor kinase (GRK) 2 determines a generalized decrease of beta-adrenergic vasodilatation. We analyzed the possibility of differential changes in the expression and functionality of alpha(1A), alpha(1B), alpha(1D), beta(1), beta(2), and beta(3)-ARs also being involved in the process. We combined the quantification of mRNA levels with immunoblotting and functional studies in aortas of young and adult spontaneously hypertensive rats (SHRs) and their controls (Wistar Kyoto). We found the expression and function of beta(1)-adrenoceptors in young prehypertensive SHRs to be higher, whereas a generalized increase in the expression of the six adrenoceptors and GRK2 was observed in aortas of adult hypertensive SHRs. alpha(1D)- and beta(3)-adrenoceptors, the subtypes that are more resistant to GRK2-mediated internalization and mostly expressed in rat aorta, exhibited an increased functional role in hypertensive animals, showing two hemodynamic consequences: 1) an increased sensitivity to the vasoconstrictor stimulus accompanied by a decreased sensitivity to the vasodilator stimulus (alpha(1D)-ARs are the most sensitive to agonists, and beta(3)-ARs are the least sensitive to agonists); and 2) a slower recovery of the basal tone after adrenergic stimulus removal because of the kinetic characteristic of the alpha(1D) subtype. These functional changes might be involved in the greater sympathetic vasoconstrictor tone observed in hypertension.
Description9 pages, 7 figures, 3 tables.-- PMID: 19060223 [PubMed]
Publisher version (URL)http://dx.doi.org/10.1124/jpet.108.146043
Appears in Collections:(IBV) Artículos
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