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This Article Full Text Full Text (PDF) All Versions of this Article: 293/4/H2140    most recent 00390.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Vinci, M. C. Articles by Parenti, A. Search for Related Content PubMed PubMed Citation Articles by Vinci, M. C. Articles by Parenti, A.

Trophic effects induced by _1D-adrenoceptors on endothelial cells are potentiated by hypoxia

Laboratory of Vascular Pharmacology, Department of Preclinical and Clinical Pharmacology, University of Florence, Florence, Italy

Submitted 29 March 2007 ; accepted in final form 26 July 2007

Catecholamines have been shown to be involved in vascular remodeling through the stimulation of ₁-adrenoceptors (₁-ARs). Recently, it has been demonstrated that catecholamines can stimulate angiogenesis in pathological conditions, even if the mechanisms and the AR subtypes involved still remain unclear. We investigated the influence of hypoxia (3% O₂) on the ability of picomolar concentrations of phenylephrine (PHE), which are unable to induce any vascular contraction, to induce a trophic effect in human endothelial cells through stimulation of the _1D-subtype ARs. PHE, at picomolar concentrations, significantly promoted pseudocapillary formation from fragments of human mature vessels in vitro. Exposure to hypoxia significantly potentiated this effect, which was inhibited by the selective _1D-AR antagonist BMY-7378 and by the nitric oxide synthase inhibitor L-NAME, suggesting that _1D-ARs were involved in this effect through activation of the nitric oxide pathway. Proliferation and migration of HUVEC were also affected by picomolar PHE concentrations. Again, these effects were significantly potentiated in cells exposed to hypoxia and were inhibited by BMY-7378 and by N^G-nitro-L-arginine methyl ester. Conversely, the _1A-AR-selective antagonist (S)-(+)-niguldipine hydrochloride and the _1B-AR antagonist chloroethylclonidine dihydrochloride did not modify endothelial cell migration and proliferation in response to PHE. These results demonstrate that the stimulation of _1D-ARs, triggered by picomolar PHE concentrations devoid of any contractile vascular effects, induces a proangiogenic phenotype in human endothelial cells that is enhanced in a hypoxic environment. The role of _1D-ARs may become more prominent in the adaptive responses to hypoxic vasculature injury.

vascular remodeling; low oxygen tension; endothelial cell growth and migration; catecholamines; nitric oxide