The role of AT-1 antagonist on wound healing in rats with hypertension and diabetes

Abstract

Wound healing is a complex process involving molecular and structural interactions. Transforming growth factor β (TGF-β), the renin-angiotensin system (RAS), and other important mediators play a central role on wound healing process. This study examined the dynamics of healing in healthy, hypertensive, and diabetic rats treated with or without Losartan, focusing on healing rate, scar characteristics, and molecular modulation. Macroscopic and microscopic analyses revealed delayed healing and reduced collagen deposition in diabetic and hypertensive rats compared with normoglycemic controls. Losartan affected healing by regulating TGF-β expression and collagen organization. In the groups of hypertensive and diabetic rats treated with losartan, healing aesthetics improved by less collagen deposition and consequently minor chances to fibrosis development, probably due to lower TGFβ and SMADs expression. Diabetic rats showed reduced skin and collagen fiber thickness, whereas hypertensive rats showed better healing under Losartan treatment (LT). These results demonstrate the complex interactions between LT, diabetes and hypertension on important fibrotic and inflammatory pathways. Although LT successfully reduces TGF-β expression and classical SMAD signaling in hypertensive settings, its minor effect in diabetes conditions indicate the necessity of supplemental treatments that target mechanisms unique to hyperglycemia, such as glycation end products or oxidative stress inhibitors. To improve treatment outcomes for individuals with diabetes and hypertension comorbidities, future studies should investigate the combination of multi-pathway modulators.