Modulation of Nitric Oxide Bioavailability Attenuates Ischemia-Reperfusion Injury in Type II Diabetes.
Animals
Arginine
/ pharmacology
Diabetes Mellitus, Experimental
/ metabolism
Diabetes Mellitus, Type 2
/ metabolism
Disease Models, Animal
Male
Nitric Oxide
/ biosynthesis
Nitric Oxide Synthase
/ pharmacology
Nitric Oxide Synthase Type I
/ pharmacology
Nitric Oxide Synthase Type II
/ pharmacology
Nitric Oxide Synthase Type III
/ pharmacology
Rats
Rats, Wistar
Reperfusion Injury
/ metabolism
Skin
/ metabolism
Surgical Flaps
/ physiology
Bioavailability
Ischemia-Reperfusion Injury
L-arginine
Microcirculation
Nitric oxide
Nitric oxide synthase
Journal
Journal of plastic, reconstructive & aesthetic surgery : JPRAS
ISSN: 1878-0539
Titre abrégé: J Plast Reconstr Aesthet Surg
Pays: Netherlands
ID NLM: 101264239
Informations de publication
Date de publication:
01 2021
01 2021
Historique:
received:
08
07
2019
revised:
31
05
2020
accepted:
01
08
2020
pubmed:
8
9
2020
medline:
3
2
2021
entrez:
7
9
2020
Statut:
ppublish
Résumé
Diabetes mellitus increases the susceptibility of free tissue transplantations to ischemia-reperfusion injury. The aim of this study was to enhance nitric oxide (NO) bioavailability through exogenous NO synthase and the substrate L-arginine to attenuate ischemia reperfusion-induced alterations in a type 2 diabetes rodent model. Sixty-four Wistar rats were divided into 8 experimental groups. Type 2 diabetes was established over 3 months with a combination of a high-fat diet and streptozotocin. A vascular pedicle isolated rat skin flap model that underwent 3 h of ischemia was used. At 30 min before ischemia, normal saline, endothelial NOSs (eNOSs), inducible NOSs, neuronal NOSs (1 and 2 IU), and L-arginine (50 mg/kg body weight) were administered by intravenous infusion alone or in combination. Ischemia-reperfusion-induced alterations were measured 5 days after the operation. The three isoforms of NOS significantly increased the flap vitality rate (VR) between 20% and 28% as compared to the control group (3%). Sole L-arginine administration increased the VR to 33%. The combination of L-arginine with NOS resulted in a further increase in flap VRs (39%-50%). Best results were achieved with the combination of eNOS and L-arginine (50%). An increase in enzyme dosage led to decreased VRs in all NOS isoforms alone and even in combination with L-arginine. Modulation of NO bioavailability through the exogenous application of NOSs and L-arginine significantly attenuated ischemia-reperfusion-induced alterations in a type 2 diabetic skin flap rat model. The combination of enzyme and substrate result in the highest VRs. Higher enzyme dosage seems to be less effective. This pharmacological preconditioning could be an easy and effective interventional strategy to support the conversion of L-arginine to NO in ischemic and in type 2 diabetic conditions.
Sections du résumé
BACKGROUND
Diabetes mellitus increases the susceptibility of free tissue transplantations to ischemia-reperfusion injury. The aim of this study was to enhance nitric oxide (NO) bioavailability through exogenous NO synthase and the substrate L-arginine to attenuate ischemia reperfusion-induced alterations in a type 2 diabetes rodent model.
MATERIAL AND METHODS
Sixty-four Wistar rats were divided into 8 experimental groups. Type 2 diabetes was established over 3 months with a combination of a high-fat diet and streptozotocin. A vascular pedicle isolated rat skin flap model that underwent 3 h of ischemia was used. At 30 min before ischemia, normal saline, endothelial NOSs (eNOSs), inducible NOSs, neuronal NOSs (1 and 2 IU), and L-arginine (50 mg/kg body weight) were administered by intravenous infusion alone or in combination. Ischemia-reperfusion-induced alterations were measured 5 days after the operation.
RESULTS
The three isoforms of NOS significantly increased the flap vitality rate (VR) between 20% and 28% as compared to the control group (3%). Sole L-arginine administration increased the VR to 33%. The combination of L-arginine with NOS resulted in a further increase in flap VRs (39%-50%). Best results were achieved with the combination of eNOS and L-arginine (50%). An increase in enzyme dosage led to decreased VRs in all NOS isoforms alone and even in combination with L-arginine.
CONCLUSION
Modulation of NO bioavailability through the exogenous application of NOSs and L-arginine significantly attenuated ischemia-reperfusion-induced alterations in a type 2 diabetic skin flap rat model. The combination of enzyme and substrate result in the highest VRs. Higher enzyme dosage seems to be less effective. This pharmacological preconditioning could be an easy and effective interventional strategy to support the conversion of L-arginine to NO in ischemic and in type 2 diabetic conditions.
Identifiants
pubmed: 32893152
pii: S1748-6815(20)30348-X
doi: 10.1016/j.bjps.2020.08.021
pii:
doi:
Substances chimiques
Nitric Oxide
31C4KY9ESH
Arginine
94ZLA3W45F
Nitric Oxide Synthase
EC 1.14.13.39
Nitric Oxide Synthase Type I
EC 1.14.13.39
Nitric Oxide Synthase Type II
EC 1.14.13.39
Nitric Oxide Synthase Type III
EC 1.14.13.39
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
183-191Informations de copyright
Copyright © 2020. Published by Elsevier Ltd.
Déclaration de conflit d'intérêts
Declaration of Competing Interest None declared.