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β2-adrenoreceptors control human skin microvascular reactivity

  • Investigative Report
  • Published:
European Journal of Dermatology

Abstract

Background

Topical αd- 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.

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Acknowledgments and disclosures

This work was supported by the grants SAF2017-82913-R (JC), Fondo Europeo de Desarrollo Regional (FEDER) and Instituto de salud carlos III FIS PI17/02158 (JM), JR18/00050 (JM), PI20/01363 (JM), CIBERES (CB06/06/0027) and TRACE (TRA2009-0311) from the Spanish Government and by research grants from the Regional Government Prometeo 2017/023/UV (JC), from “Generalitat Valenciana”. Funding entities did not contribute to the study design or data collection, analysis and interpretation nor to the writing of the manuscript. Conflicts of interest: none.

Author information

Authors and Affiliations

  1. Department of Pharmacology, Faculty of Medicine, University of Valencia, Valencia, Spain

    Anselm Morell, Javier Milara & Julio Cortijo

  2. CIBERES, Health Institute Carlos III, Valencia, Spain

    Javier Milara & Julio Cortijo

  3. University Jaume I, Castellon, Spain

    Javier Milara

  4. Pharmacy Unit, General University Hospital, Valencia, Spain

    Javier Milara

  5. Servicio de medicina física y rehabilitación hospital general universitario, Castellón, Spain

    Laurabel Gozalbes

  6. Research & Development Center, Almirall, Sant Feliu de Llobregat, Barcelona, Spain

    Amedeu Gavaldà, Gema Tarrasón & Nuria Godessart

  7. Plastic Surgery Unit, University General Hospital Consortium, Valencia, Spain

    Severiano Marín

  8. Urology department, Hospital casa de la Salud, Valencia, Spain

    Pedro Navalón

  9. Research and teaching Unit, University General Hospital Consortium, Valencia, Spain

    Julio Cortijo

Authors
  1. Anselm Morell
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Correspondence to Javier Milara.

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Morell, A., Milara, J., Gozalbes, L. et al. β2-adrenoreceptors control human skin microvascular reactivity. Eur J Dermatol 31, 326–334 (2021). https://doi.org/10.1684/ejd.2021.4068

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  • DOI: https://doi.org/10.1684/ejd.2021.4068

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