PMID- 37979830 OWN - NLM STAT- MEDLINE DCOM- 20231216 LR - 20231216 IS - 1879-0712 (Electronic) IS - 0014-2999 (Linking) VI - 961 DP - 2023 Dec 15 TI - Desmopressin enhances random-pattern skin flap survival in rats: Possible role of vasopressin Type-1a and 2 receptors. PG - 176203 LID - S0014-2999(23)00717-3 [pii] LID - 10.1016/j.ejphar.2023.176203 [doi] AB - BACKGROUND: Many drugs have been explored for their role in improving skin flap survival. 1-deamino-8-D-arginine vasopressin (DDAVP or desmopressin) is a synthesized form of anti-diuretic hormone (ADH) and a selective agonist for vasopressin type-2 receptors (V2 receptors). Desmopressin has been shown to improve endothelial function, induce vasodilation, and reduce inflammation. We aimed to evaluate its efficacy in enhancing flap survival and assess the role of vasopressin receptors in this process. MATERIALS AND METHODS: We randomly assigned six male Wistar rats to each study group. Different doses of desmopressin were injected intraperitoneally to find the most effective amount (8 mug/rat). SR-49059, a selective V1a receptor antagonist, was given at 2mug/rat before providing the most effective dose of desmopressin (8mug/rat). Histopathological assessments, quantitative measurements of interleukin-1beta (IL-1beta), Tumor necrosis factor-alpha (TNF-alpha), and Nuclear Factor-kappaB (NF-kappaB), optical imaging, and measurement of the expression levels of V2 receptor in the rat skin tissue were performed. RESULTS: Desmopressin (8mug/rat) significantly reduced the mean percentage of necrotic area compared to the control group (19.35% vs 73.57%). Histopathological evaluations revealed a notable reduction in tissue inflammation, edema, and degeneration following administration of desmopressin (8). The expression of the V2 receptor was increased following desmopressin administration. It also led to a reduction in IL-1beta, TNF-alpha, and NF-kappaB levels. The protective effect of desmopressin on flap survival was reversed upon giving SR-49059. The optical imaging revealed enhanced blood flow in the desmopressin group compared to the control group. CONCLUSIONS: Desmopressin could be repurposed to improve flap survival. V1a and V2 receptors probably mediate this effect. CI - Copyright (c) 2023 Elsevier B.V. All rights reserved. FAU - Farhangi, Pourya AU - Farhangi P AD - Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran; School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. FAU - Kaveh, Meysam AU - Kaveh M AD - Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran; School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. FAU - Afrooghe, Arya AU - Afrooghe A AD - Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran; School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. FAU - Jafari, Razieh Mohammad AU - Jafari RM AD - Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran; Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: rmjafari@sina.tums.ac.ir. FAU - Aryannejad, Armin AU - Aryannejad A AD - Division of Experimental Pathology, Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Pittsburgh Liver Research Center, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. FAU - Mashinchi, Baharnaz AU - Mashinchi B AD - Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran; School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. FAU - Rezaie, Yasaman AU - Rezaie Y AD - Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran; School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. FAU - Abdollahi, Alireza AU - Abdollahi A AD - Department of Pathology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. FAU - Dehpour, Ahmad-Reza AU - Dehpour AR AD - Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran; Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: dehpour@yahoo.com. LA - eng PT - Journal Article DEP - 20231116 PL - Netherlands TA - Eur J Pharmacol JT - European journal of pharmacology JID - 1254354 RN - ENR1LLB0FP (Deamino Arginine Vasopressin) RN - 0 (Receptors, Vasopressin) RN - 0 (NF-kappa B) RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (Antidiuretic Hormone Receptor Antagonists) RN - 11000-17-2 (Vasopressins) SB - IM MH - Rats MH - Male MH - Animals MH - *Deamino Arginine Vasopressin/pharmacology MH - *Receptors, Vasopressin/physiology MH - NF-kappa B MH - Tumor Necrosis Factor-alpha MH - Rats, Wistar MH - Antidiuretic Hormone Receptor Antagonists MH - Vasopressins/pharmacology MH - Inflammation OTO - NOTNLM OT - Desmopressin OT - Inflammation OT - Rat OT - Skin flap OT - Vasopressin receptors COIS- Declaration of competing interest This letter is to certify that the authors declare that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper. EDAT- 2023/11/19 09:42 MHDA- 2023/12/17 09:43 CRDT- 2023/11/18 19:31 PHST- 2023/09/12 00:00 [received] PHST- 2023/11/03 00:00 [revised] PHST- 2023/11/10 00:00 [accepted] PHST- 2023/12/17 09:43 [medline] PHST- 2023/11/19 09:42 [pubmed] PHST- 2023/11/18 19:31 [entrez] AID - S0014-2999(23)00717-3 [pii] AID - 10.1016/j.ejphar.2023.176203 [doi] PST - ppublish SO - Eur J Pharmacol. 2023 Dec 15;961:176203. doi: 10.1016/j.ejphar.2023.176203. Epub 2023 Nov 16.