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

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 beta- and alpha-adrenoceptor blockade on cutaneous wound healing. Male rats were treated with propranolol (beta1- and beta2-antagonist), atenolol (beta1-antagonist), or phentolamine (alpha1- and alpha2-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 alpha-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. beta1- and beta2-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. alpha1- and alpha2-adrenoceptor blockade only affected leukocyte migration, epithelial and connective tissue cell proliferation, and pro-MMP-9 levels. In conclusion, beta-1 and beta-2, but not alpha-1 and alpha-2, adrenoceptor blockade delays cutaneous wound healing.

Pharmacological targeting of β-adrenergic receptor functions abrogates NF-κB signaling and MMP-9 secretion in medulloblastoma cells

“…Whether β-adrenergic blockade would be involved remains to be determined. In support of our current data with brain tumor cells, β 2 -adrenergic antagonists suppressed pancreatic cancer cell invasion by inhibiting NF-κB and MMP-9 expression, 49 while MMP-9 levels were decreased upon β 1 - and β 2 -adrenoceptor blockade 50. In summary, our data are indicative of a role for propranolol against carcinogen-mediated signaling that leads to the secretion of the BBB disruptor enzyme MMP-9.…”

Evaluation of Therapeutic Intervention with a Natural Product in Cutaneous Wound Healing: The Use of Capybara Oil

“…During reepithelialization, keratinocyte proliferation ensures that there is an adequate supply of cells to migrate into and cover the wound [1]; however, keratinocyte proliferation may occur independently of keratinocyte migration during reepithelialization [16]. Furthermore, during the dermal reconstruction by granulation tissue formation, the fibroblasts proliferate and subsequently migrate to the wounded area and then deposit and organize the ECM [1].…”

“…Photomicrographs were captured for the analysis of collagen fibers in the wounded area. The picrosirius red method highlights the birefringence of normal collagen fibers; thick fibers appear strongly birefringent and yellow-to-red in color, whereas thin collagen fibers are weakly birefringent and greenish [16]. Fibers of the microfibril-elastin system were stained with Weigert's resorcin fuchsin, and for the analysis of elastic fibers in the wounded area, several photomicrographs were observed and captured by a videomicroscopic system.…”

Dual targeting of TNF-αand free radical toxic stress as a promising strategy to manage experimental polycystic ovary

“…In that regard, the blocking effect of carvedilol on b-adrenergic receptors has been indicated to decrease the concentrations of MMP-2 and MMP-9 (Ohtsuka et al, 2003;Romana-Souza et al, 2009). Altogether, considering the prominent role of b-adrenergic stimulation as an activator of the sympathetic nerves in women with PCO, carvedilol therapy could be put into practice to manage PCO(S) complications.…”