Side Effects of Frequently Used Antihypertensive Drugs on Wound Healing in vitro

Abstract

Background: The number of patients who has a daily intake of antihypertensive drugs is rising, due to an also rising prevalence of lifestyle diseases. Interestingly, knowledge about effects of these drugs in terms of wound healing is low. Objective: Based on a few differing studies, the idea arose that antihypertensives may have side effects on wound healing. Methods: Five antihypertensive drugs from different substance classes (metoprolol, amlodipine, ramipril, hydrochlorothiazide, candesartan) were investigated, in terms of possible impacts on cell metabolism and migration of human skin fibroblasts and keratinocytes. Additionally, histological and immunohistochemical analyses were performed in a 3-dimensional (3D) wound model addressing the influence on regeneration processes, such as cell migration, metabolic activity, apoptosis and epidermal thickness. Results: Hydrochlorothiazide and ramipril exerted inhibiting effects in nearly all analyses, interestingly, in serum equivalent doses. In contrast, candesartan and amlodipine induced slight positive effects in 2D as well as in 3D models. The previously described positive effects of β-blockers could only partially be confirmed by metoprolol. Antihypertensive drugs affected fibroblasts more than keratinocytes – whether positively or negatively. Conclusion: Antihypertensive drugs have an influence on keratinocytes and fibroblasts; they are not neutral. Candesartan has the most positive effects on skin cells. For angiotensin-converting enzyme inhibitors and thiazide diuretics, wound healing in a 3D model is delayed. β-Receptor blockers seem to improve wound healing to a small extent just like calcium channel blockers. These results should be evaluated in a clinical trial to verify their clinical relevance.

Antihypertensive Effects of Polyphenolic Extract from Korean Red Pine (Pinus densiflora Sieb. et Zucc.) Bark in Spontaneously Hypertensive Rats

“…CAP down-regulated the expression of the insulin-like growth factor receptor and phosphorylated mitogen-activated protein kinases, resulting in decreased collagen synthesis [39]. In addition, ramipril has been reported to increase the expression of caspase 3 in fibroblasts in a 3D wound model and adversely affects wound healing [40]. In contrast, many phenolics with antioxidant capacity have been known to promote wound healing by regulating the inflammatory stage of the wound healing process by scavenging ROS [41].…”

The Response and Tolerability of a Novel Cold Atmospheric Plasma Wound Dressing for the Healing of Split Skin Graft Donor Sites: A Controlled Pilot Study

“…Every other day, during replacement of wound dressings, we measured deep tissue oxygen saturation (i.e., near-infrared [NIR] perfusion), superficial hemoglobin oxygen saturation (StO 2 ), hemoglobin distribution (i.e., tissue hemoglobin index [THI]), and tissue water distribution (i.e., tissue water index [TWI]) using a modern hyperspectral imaging (HSI) camera device [19][20][21]. These parameters provide insights into the biological mechanisms of the healing process and, thus, allow a quantification in the context of the 3 stages of wound healing: inflammation, proliferation, and remodeling [22][23][24].…”

Lipid emulsion attenuates extrinsic apoptosis induced by amlodipine toxicity in rat cardiomyoblasts

“…2 –5,9,10 Amlodipine toxicity results in a negative inotropic effect and bradycardia in isolated heart preparation, and apoptosis in uveal malignant melanoma and human fibroblasts. 11 –14 A previous study showed that lipid emulsion attenuated apoptosis in cardiomyoblasts induced by the phenylalkylamine calcium channel blocker verapamil at toxic doses. 15 It has been reported that phosphoinositide-3 kinase and ATP-sensitive potassium channels are involved in cardiac protection.…”