Histological evaluation of the effects of angiotensin peptides on wound repair in diabetic mice

Recent studies have shown that angiotensin peptides accelerate dermal repair. Histological observation of samples taken at the termination of studies showed that the wounds treated with peptides were more mature and organized by day 25 after full thickness excision in diabetic mice. However, the mechanism by which this acceleration occurs has not been determined. In the experiments described here, the effect of angiotensin peptides [AII, A(1-7) and NorLeu³-A(1-7)] on the quality of the healing wound was evaluated histologically. Administration of the peptides accelerated collagen deposition, re-epithelialization and new blood vessel formation. By day 4, the percentage of the wound with collagen increased two- to six-fold depending upon the peptide. The increase by angiotensin peptides continued throughout the experimental period. On days 4 and 7 (only) after injury, exposure to angiotensin peptides increased the number of blood vessels at the wound site two- to three-fold. Finally, the percentage of the wound site covered with new epithelium increased after administration of angiotensin peptides. Re-epithelialization was observed as early as day 4 in wounds treated with angiotensin peptides. The increase was greater at later time points [up to 8-fold at day 14 with NorLeu³-A(1-7)]. Fibroblast infiltration and proliferation occurred earlier in wounds treated with angiotensin peptides. Wounds treated with A(1-7) and NorLeu³-A(1-7) had an increase in neutrophils and macrophages on day 4 after wounding. Overall, administration of these peptides resulted in a healing site that was more mature, including reorganization of the collagen into a basket-weave appearance. Further, these studies confirm the superiority of NorLeu³-A(1-7) to AII and A(1-7) in wound healing evaluated at a microscopic level.