Acceleration of dermal tissue repair by angiotensin II.

ABSTRACT

Angiotensin II is a naturally occurring peptide which has been shown to possess angiogenic properties. In the studies reported here, angiotensin II was shown to increase the proliferation of cultured bovine aortic arch endothelial cells in a concentration-dependent manner. Acute administration of angiotensin II in Hydron accelerated the repair of dermal injuries in a full-thickness excisional rat model. Additional studies were done to determine the best vehicle for delivery of angiotensin II to a dermal injury. Several vehicles, including 10% low-viscosity carboxymethyl cellulose, 4% medium-viscosity carboxymethyl cellulose, and 3% high-viscosity carboxymethyl cellulose, were found to be effective in this regard. Daily administration of angiotensin II for days 0 to 4 after injury (day 0 being the time of surgery) was determined to provide the optimal dosage for acceleration of wound repair by angiotensin II. In addition, dose-response studies indicated that angiotensin II accelerated wound repair in a dose-dependent fashion with 0.03 and 0.01 microg/rat/day of angiotensin II administered on days 0 to 4 being the minimally effective and no-effect doses, respectively. Administration of 100 microg/day of angiotensin II in 10% carboxymethyl cellulose for 5 days after injury to animals with impaired healing (steroid- and adriamycin-treated rats and diabetic mice) was also found to accelerate the rate of repair. In conclusion, angiotensin II accelerated the closure of full-thickness skin injuries in a dose-dependent manner in normal and impaired animal models.