1. The participation of sympathetic efferent fibres in wound healing is not well understood. The aim of the present study was to investigate the effects of beta(1)- and beta(2)-adrenoceptor blockade on rat excisional cutaneous wound healing. 2. Male rats were treated orally with propranolol dissolved in drinking water (50 mg/kg per day), whereas the control group received drinking water without propranolol. Propranolol was administered daily until rats were killed. A full-thickness excisional lesion was performed. The lesion area was measured to evaluate wound contraction. After rats had been killed, lesion and adjacent normal skin were formol fixed and paraffin embedded. Sections were stained with haematoxylin-eosin, Sirius red or Toluidine blue and immunostained for a-smooth muscle actin or proliferating cell nuclear antigen. 3. Propranolol-treated rats presented delayed wound contraction and epidermal healing and decreased hydroxyproline levels, collagen density and neo-epidermis thickness. Blockade of beta(1)- and beta(2)-adrenoceptors increased epidermal and connective tissue cell proliferation, polymorphonuclear leucocyte migration, myofibroblast density and mast cell migration. The volume density of blood vessels was increased and vessels were more dilated in propranolol-treated animals. 4. Thus, we conclude that beta(1)- and beta(2)-adrenoceptor blockade impairs cutaneous wound healing. This information should be considered by physicians during the treatment of patients who present with hypertension and problems in the healing process (such as venous ulcers).

Participation of the peripheral nervous system in wound healing is not well understood. The aim of this study was to investigate the effects of sympathetic denervation on rat excisional cutaneous wound healing. Male rats were chemically denervated with intraperitoneal administration of 6-hydroxydopamine (6-OHDA) in 1% ascorbic acid. 6-OHDA or vehicle was administered twice a week until euthanasia, beginning 7 days before wounding. A full-thickness excisional lesion was performed and the lesion area measured to evaluate wound contraction. After euthanasia, the lesion and adjacent normal skin were formalin-fixed and paraffin-embedded. Sections were stained with hematoxylin and eosin or toluidine blue, or immunostained for alpha-smooth muscle actin. Animals treated with 6-OHDA showed acceleration in wound contraction, increase in myofibroblastic differentiation, reduction in mast cell migration, and a delay in reepithelialization. To investigate the effects of neurogenic inflammation, a group of animals was treated with 6-OHDA only after the acute inflammatory phase, and these animals showed delayed wound contraction 3 and 7 days after wounding when compared to those treated before the lesion. In conclusion, the present study shows that sympathetic denervation affects cutaneous wound healing, probably by a decrease in neurogenic inflammation during the initial phase of healing and the absence of catecholamines throughout the final phase.

It has been clinically and experimentally shown that cigarette smokers suffer from impaired wound healing, but the mechanisms that lead to the alterations are not well understood. The aim of this study was to investigate if the effects of cigarette smoke exposure on excisional cutaneous wound healing are different depending on the strain (Swiss, BALB/c and C57BL/6 mice) studied. Male mice were exposed to smoke of nine whole cigarettes per day, 3 times/day, daily, for 10 days. In the 11th day a full-thickness excisional wound was performed. Control group was sham-exposed and also had a full-thickness excisional wound. The cigarette smoke exposure protocol was performed until euthanasia. Animals were euthanatized 14 days after wounding. Wound contraction was evaluated 7 and 14 days after lesion. Sections were stained with hematoxylin-eosin, Sirius red or toluidine blue and immunostained for alpha-smooth muscle actin. Smoke exposed animals presented delay in wound contraction, in fibroblastic and inflammatory cells recruitment and in myofibroblastic differentiation; those alterations were strain dependent. Cigarette smoke exposure also affected mast cells recruitment and neoepidermis thickness. In conclusion, the present study demonstrated that the effects of cigarette smoke in mice cutaneous wound healing are related to mice strain studied.

Grasslands are the largest contributor of nitrous oxide (N2O) emissions in the agriculture sector due to livestock excreta and nitrogen fertilizers applied to the soil. Nitrification inhibitors (NIs) added to N input have reduced N2O emissions, but can show a range of efficiencies depending on climate, soil, and management conditions. A meta-analysis study was conducted to investigate the factors that influence the efficiency of NIs added to fertilizer and excreta in reducing N2O emissions, focused on grazing systems. Data from peer-reviewed studies comprising 2164 N2O emission factors (EFs) of N inputs with and without NIs addition were compared. The N2O EFs varied according to N source (0.0001–8.25%). Overall, NIs reduced the N2O EF from N addition by 56.6% (51.1–61.5%), with no difference between NI types (Dicyandiamide—DCD; 3,4-Dimethylpyrazole phosphate—DMPP; and Nitrapyrin) or N source (urine, dung, slurry, and fertilizer). The NIs were more efficient in situations of high N2O emissions compared with low; the reduction was 66.0% when EF > 1.5% of N applied compared with 51.9% when EF ≤ 0.5%. DCD was more efficient when applied at rates > 10 kg ha−1. NIs were less efficient in urine with lower N content (≤ 7 g kg−1). NI efficiency was negatively correlated with soil bulk density, and positively correlated with soil moisture and temperature. Better understanding and management of NIs can optimize N2O mitigation in grazing systems, e.g., by mapping N2O risk and applying NI at variable rate, contributing to improved livestock sustainability.