| Autor: |
Morell A; Department of Pharmacology, Faculty of Medicine, University of Valencia, Spain., Milara J; Department of Pharmacology, Faculty of Medicine, University of Valencia, Spain, CIBERES, Health Institute Carlos III, Valencia, Spain, University Jaume I, Castellon, Spain, Pharmacy Unit, General University Hospital, Valencia, Spain., Gozalbes L; Servicio de medicina física y rehabilitación hospital general universitario, Castellón, Spain., Gavaldà A; Almirall, Research & Development Center, Sant Feliu de Llobregat, Barcelona, Spain., Tarrasón G; Almirall, Research & Development Center, Sant Feliu de Llobregat, Barcelona, Spain., Godessart N; Almirall, Research & Development Center, Sant Feliu de Llobregat, Barcelona, Spain., Marín S; Plastic Surgery Unit, University General Hospital Consortium, Valencia, Spain., Navalón P; Urology department, Hospital casa de la Salud, Valencia, Spain., Cortijo J; Department of Pharmacology, Faculty of Medicine, University of Valencia, Spain, CIBERES, Health Institute Carlos III, Valencia, Spain, Research and teaching Unit, University General Hospital Consortium, Valencia, Spain. |
| Abstrakt: |
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. 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). 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. 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. |
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