Stress-induced epinephrine levels compromise murine dermal fibroblast activity through β-adrenoceptors

Stress-induced catecholamine impairs the formation of granulation tissue acting directly in fibroblast activity; however, the mechanism by which high levels of catecholamines alter the granulation tissue formation is still unclear. Thus, the aim of this study was to investigate how high levels of epinephrine compromise the activity of murine dermal fibroblasts. Dermal fibroblasts isolated from the skin of neonatal Swiss mice were preincubated with alpha- or beta-adrenoceptor antagonists. Thereafter, cells were exposed to physiologically elevated levels of epinephrine or epinephrine plus alpha- or beta-adrenoceptor antagonists, and fibroblast activity was evaluated. The blockade of beta 1- and beta 2-adrenoceptors reversed the increase in fibroblast proliferation, ERK 1/2 phosphorylation, myofibroblastic differentiation and the reduction of collagen deposition induced by epinephrine. In addition, the blockade of beta 3-adrenoceptors reversed the increase in fibroblast proliferation and nitric oxide synthesis as well as the reduction of fibroblast migration, AKT phosphorylation and active matrix metalloproteinase-2 expression induced by epinephrine. However, the blockade of alpha 1- and alpha 2-adrenoceptors did not alter the effects of epinephrine on the activity of murine dermal fibroblasts. In conclusion, high levels of epinephrine directly compromise the activity of neonatal mouse skin fibroblasts through the activation of beta 1-, beta 2- and beta 3-adrenoceptors, but not through alpha 1- and alpha 2-adrenoceptors.