Tissue Eng Regen Med.  2021 Feb;18(1):179-186. 10.1007/s13770-020-00308-x.

Nitric Oxide Produced by the Antioxidant Activity of Verapamil Improves the Acute Wound Healing Process

  • 1Department of Biomedicine and Health Sciences, College of Medicine, The Catholic University of Korea, 222 Banpodaero, Seoul 06591, Republic of Korea
  • 2Department of Plastic and Reconstructive Surgery, College of Medicine, Seoul St. Mary’s Hospital, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 06591, Republic of Korea
  • 3Department of Plastic and Reconstructive Surgery, College of Medicine, Yeouido St. Mary’s Hospital, The Catholic University of Korea, 1661-7575, Yeongdeungpo-gu, Seoul, Republic of Korea


Verapamil is used in the treatment of hypertension, angina pectoris, cardiac arrhythmia, hypertrophic scars, and keloids to block transmembrane calcium ion flux. Verapamil has antioxidant activity, which enhances the production of nitric oxide (NO). NO promotes the proliferation of fibroblasts, keratinocytes, endothelial cells, and epithelial cells during wound healing. In this study, we investigated the effect of verapamil and its antioxidant properties on the enhancement of acute wound healing via NO.
A full-thickness wound healing model was created on the rat dorsal with a silicone ring. The wound closure rate was estimated every 2 days for 14 days. A histological study was performed to evaluate wound healing. Immunofluorescence staining was analyzed for angiogenesis. The expressions of collagen type I (COL I), collagen type III (COL III), and vascular endothelial growth factor (VEGF) were assessed by Western blot. Real-time polymerase chain reaction (qRT-PCR) was performed to examine the expression of endothelial NO synthase and inducible NO synthase, which are related to antioxidant activity in the process of wound healing.
The wound closure rate was faster in the verapamil group compared to the control and silicone groups. Histologic analysis revealed capillaries and stratum basale in the verapamil group. Immunofluorescence staining was shown vessel formation in the verapamil group. Western blot and qRT-PCR analysis revealed high expression levels of COL I, VEGF, eNOS, and FGF in the verapamil.
Verapamil’s antioxidant activity enhances NO production in acute wound healing. We suggest that verapamil can be used to promote acute wound healing.


Antioxidant activity; Nitric oxide; Verapamil; Wound healing
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