John Libbey Eurotext

European Journal of Dermatology

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β2-adrenoreceptors control human skin microvascular reactivity Article à paraître

Illustrations

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Auteurs
1 Department of Pharmacology, Faculty of Medicine, University of Valencia, Spain
2 CIBERES, Health Institute Carlos III, Valencia, Spain
3 University Jaume I, Castellon, Spain
4 Pharmacy Unit, General University Hospital, Valencia, Spain
5 Servicio de medicina física y rehabilitación hospital general universitario, Castellón, Spain
6 Almirall, Research & Development Center, Sant Feliu de Llobregat, Barcelona, Spain
7 Plastic Surgery Unit, University General Hospital Consortium, Valencia, Spain
8 Urology department, Hospital casa de la Salud, Valencia, Spain
9 Research and teaching Unit, University General Hospital Consortium, Valencia, Spain
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Background

Topical α1- and α2-adrenoreceptor (ADRA1 and 2) agonists are effective in alleviating permanent vasodilation and facial erythema associated with rosacea by inducing skin vasoconstriction. Although β-adrenoreceptor (ADRB) antagonists are used off-label for rosacea, pharmacological and pharmacodynamic data pertaining to these receptors in skin micro-vessels are lacking. Objectives: To analyse the expression of different adrenergic receptors and their contribution to vasoreactivity in skin micro-vessels.

Materials & Methods

Small arteries (500–800 μm) and arterioles (<200 μm) were studied in human foreskin tissue. Specifically, ADR-A1, -A2, -B1 and -B2 expression was assayed by immunofluorescence, polymerase chain reaction (PCR), and western blotting. Small skin artery reactivity was evaluated using ex vivo myography (500–800 μm) or a visible microscope perfusion system with precision-cut skin slices (<200 μm).

Results

ADRB2 was the most highly expressed receptor in small skin arteries and arterioles, followed by ADRA2. ADRA2 activation via brimonidine-induced vasoconstriction was greater in skin arterioles than in small skin arteries, and more potent than that with norepinephrine (NE). The use of prazosin (ADRA1 inhibitor) partially attenuated brimonidine-induced vasoconstriction, indicating some activation of ADRA1 by brimonidine, at least at 10-μM concentrations. Small skin arteries and arterioles, pre-treated with prazosin and stimulated with NE, exhibited ADRB2-mediated vasodilation, which was inhibited by the beta blockers, propranolol or timolol.

Conclusion

This study shows that ADRB2 is predominantly expressed in small skin arteries and arterioles, and that ADRBs plays a functional role in vasodilation. The data presented here indicate that ADRBs can be a therapeutic target for the treatment of rosacea.