β-1 and β-2, but not α-1 and α-2, adrenoceptor blockade delays rat cutaneous wound healing

• Published in: Wound repair and regeneration 2009-03, Vol.17 (2), p.230-239
• Main Authors: Romana-Souza, Bruna, Santos, Jeanine S., Monte-Alto-Costa, Andréa
• Format: Article
• Language: English
• Subjects: Adrenergic alpha-1 Receptor Antagonists; Adrenergic alpha-2 Receptor Antagonists; Adrenergic alpha-Antagonists - pharmacology; Adrenergic beta-1 Receptor Antagonists; Adrenergic beta-2 Receptor Antagonists; Adrenergic beta-Antagonists - pharmacology; Animals; Atenolol - pharmacology; Disease Models, Animal; Granulation Tissue - physiology; Immunohistochemistry; Male; Phentolamine - pharmacology; Propranolol - pharmacology; Rats; Rats, Wistar; Receptors, Adrenergic, alpha-1 - drug effects; Receptors, Adrenergic, alpha-1 - physiology; Receptors, Adrenergic, alpha-2 - drug effects; Receptors, Adrenergic, alpha-2 - physiology; Receptors, Adrenergic, beta-1 - drug effects; Receptors, Adrenergic, beta-1 - physiology; Receptors, Adrenergic, beta-2 - drug effects; Receptors, Adrenergic, beta-2 - physiology; Skin - injuries; Statistics, Nonparametric; Wound Healing - physiology
• ISSN: 1067-1927; 1524-475X
• DOI: 10.1111/j.1524-475X.2008.00453.x

ABSTRACT The sympathetic nervous system plays an important role in wound healing, but its mechanism of action is poorly understood. The aim of this study was to investigate the effects of β‐ and α‐adrenoceptor blockade on cutaneous wound healing. Male rats were treated with propranolol (β1‐ and β2‐antagonist), atenolol (β1‐antagonist), or phentolamine (α1‐ and α2‐antagonist) dissolved in drinking water. A full‐thickness excisional lesion was created and the wound area was measured. Fourteen days after wounding, lesions and adjacent skin were removed, formalin‐fixed, and paraffin‐embedded. Sections were stained with hematoxylin–eosin and toluidine blue, and immunostained for α‐smooth muscle actin and proliferating cell nuclear antigen. Wound contraction was delayed in propranolol‐ and atenolol‐treated animals but not in phentolamine‐treated animals. Reepithelialization was decreased only in propranolol‐treated animals. β1‐ and β2‐adrenoceptor blockade delayed leukocyte migration, epidermal and connective tissue cell proliferation, myofibroblastic differentiation, and mast cell migration. The volume density of blood vessels was increased in the propranolol‐ and atenolol‐treated animals compared with controls. The levels of matrix metalloproteases (MMP‐2 and MMP‐9) decreased in the propranolol‐ and atenolol‐treated animals. α1‐ and α2‐adrenoceptor blockade only affected leukocyte migration, epithelial and connective tissue cell proliferation, and pro‐MMP‐9 levels. In conclusion, β‐1 and β‐2, but not α‐1 and α‐2, adrenoceptor blockade delays cutaneous wound healing.