Int J Med Sci 2021; 18(4):975-983. doi:10.7150/ijms.50197 This issue

Research Paper

Angiotensin-Converting Enzyme Inhibitor, Captopril, Improves Scar Healing in Hypertensive Rats

Eun Young Rha, Jae Won Kim, Jun Hyeok Kim, Gyeol Yoo

Department of Plastic and Reconstructive Surgery, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea

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Rha EY, Kim JW, Kim JH, Yoo G. Angiotensin-Converting Enzyme Inhibitor, Captopril, Improves Scar Healing in Hypertensive Rats. Int J Med Sci 2021; 18(4):975-983. doi:10.7150/ijms.50197. Available from

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Pathological cutaneous scars, with aberrant extracellular matrix accumulation, have multiple origins. Antihypertensive medications, such as calcium channel blockers, have been used to treat pathological scars. However, a relationship between angiotensin-converting enzyme (ACE) inhibitors, pathological scars, and blood pressure (BP) has never been reported. Here, we aimed to compare the differences in scar development and the effects of the administration of systemic ACE inhibitor on scar tissue in a normotensive rat, the Wistar Kyoto rat (WKY), a hypertensive rat, and the spontaneously hypertensive rat (SHR). Using an 8-mm punch, we created two full-thickness skin defects in a total of 32 rats (16 WKY and 16 SHR) to obtain a total of 64 wounds. We established control WKY (n = 16), captopril-treated WKY (n = 16), control SHR (n = 16), and captopril-treated SHR (n = 16) groups and started captopril (100 mg/g per day) treatment on day 21 in the appropriate groups. The BP of all groups was measured at 0, 3, and 5 weeks. The scar area was measured by histopathological examination, and scarring was expressed in terms of scar area and fibroblast and capillary counts. The expression of heat shock protein (HSP) 47, type I and III collagens, alpha-smooth muscle actin (α-SMA), Ki67, and vascular endothelial growth factor (VEGF) was investigated using immunohistochemistry. The scar area and fibroblast count were significantly higher in control SHR than in control WKY. The scar area, fibroblast count, and capillary count were significantly smaller in captopril-treated SHR than in control SHR. Immunostaining for α-SMA, Ki67, and VEGF also showed a noticeable decrease in scarring in the treated SHR compared with that in control SHR. Thus, BP affects scar development in a rat model, and an ACE inhibitor is more effective at reducing scars in hypertensive rats than in normotensive rats.

Keywords: angiotensin-converting enzyme inhibitor, Wistar Kyoto rat, spontaneously hypertensive rat, scar area, fibrosis, vascular endothelial growth factor