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Inducible Nitric Oxide Synthase and L-Arginine Optimizes Nitric Oxide Bioavailability in Ischemic Tissues Under Diabetes Mellitus Type 1.
Ann Plast Surg 2020; 84(1):106-112AP

Abstract

BACKGROUND

The mechanisms influencing the balance of nitric oxide (NO) bioavailability in tissues are negatively affected under diabetic and also under ischemic conditions. Free tissue transplantation for diabetic patients has to deal with both ischemic and diabetic circumstances, which lead to a significantly decrease in providing NO, thus increasing ischemia-reperfusion injury. In previous studies, we could prove that enhancing NO bioavailability leads to attenuated ischemia-reperfusion injury macrocirculatory and microcirculatory alterations in healthy and also in diabetes type 2 rats. This study is evaluating the role of inducible nitric oxide synthase in different dosages and L-arginine under diabetes type 1 conditions.

METHODS

Diabetic type 1 conditions were established via streptozotocin over a period of 4 weeks and verified via blood sugar, insulin, and C-peptide levels. Vascular pedicle isolated rat skin flap model that underwent 3 hours of ischemia was used. At 30 minutes before ischemia, normal saline, inducible nitric oxide synthase (NOS) (1/2 IE), and L-arginine (50 mg/kg body weight) were administered systemically. Ischemia/reperfusion (I/R)-induced alterations were measured 5 days after the operation.

RESULTS

The inducible NOS (iNOS) attenuated I/R-induced alterations under diabetic type 1 conditions significantly with vitality rates of 16.1% compared with control group (5.5%). Best results could be achieved with the combination of iNOS (1 IE) and L-arginine displaying vitality rates of 43%. Increased dosage of inducible nitric oxide (2 IE) led to decreased vitality rates (22.2%/27.4% without/with L-arginine).

CONCLUSIONS

Supporting the mechanisms of NO bioavailability via exogenous application of iNOS and L-arginine significantly attenuated I/R-induced alterations in a skin flap rat model. This pharmacologic preconditioning could be an easy and effective interventional strategy to uphold conversation of L-arginine to NO even on ischemic and type 1 diabetic conditions.

Authors+Show Affiliations

From the Department of Hand, Plastic, and Reconstructive Surgery, BG Clinic Ludwigshafen, University of Heidelberg, Ludwigshafen.From the Department of Hand, Plastic, and Reconstructive Surgery, BG Clinic Ludwigshafen, University of Heidelberg, Ludwigshafen.Ethianum Clinic for Plastic and Reconstructive Surgery, Aesthetic and Preventive Medicine, Heidelberg University Hospital, Heidelberg.Ethianum Clinic for Plastic and Reconstructive Surgery, Aesthetic and Preventive Medicine, Heidelberg University Hospital, Heidelberg.Department of Neurology, DRK-Clinic Nordhessen, Kassel, Germany.From the Department of Hand, Plastic, and Reconstructive Surgery, BG Clinic Ludwigshafen, University of Heidelberg, Ludwigshafen. Ethianum Clinic for Plastic and Reconstructive Surgery, Aesthetic and Preventive Medicine, Heidelberg University Hospital, Heidelberg.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31800556

Citation

Gazyakan, Emre, et al. "Inducible Nitric Oxide Synthase and L-Arginine Optimizes Nitric Oxide Bioavailability in Ischemic Tissues Under Diabetes Mellitus Type 1." Annals of Plastic Surgery, vol. 84, no. 1, 2020, pp. 106-112.
Gazyakan E, Hirche C, Reichenberger MA, et al. Inducible Nitric Oxide Synthase and L-Arginine Optimizes Nitric Oxide Bioavailability in Ischemic Tissues Under Diabetes Mellitus Type 1. Ann Plast Surg. 2020;84(1):106-112.
Gazyakan, E., Hirche, C., Reichenberger, M. A., Germann, G., Roth, C., & Engel, H. (2020). Inducible Nitric Oxide Synthase and L-Arginine Optimizes Nitric Oxide Bioavailability in Ischemic Tissues Under Diabetes Mellitus Type 1. Annals of Plastic Surgery, 84(1), pp. 106-112. doi:10.1097/SAP.0000000000002121.
Gazyakan E, et al. Inducible Nitric Oxide Synthase and L-Arginine Optimizes Nitric Oxide Bioavailability in Ischemic Tissues Under Diabetes Mellitus Type 1. Ann Plast Surg. 2020;84(1):106-112. PubMed PMID: 31800556.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inducible Nitric Oxide Synthase and L-Arginine Optimizes Nitric Oxide Bioavailability in Ischemic Tissues Under Diabetes Mellitus Type 1. AU - Gazyakan,Emre, AU - Hirche,Christoph, AU - Reichenberger,Matthias A, AU - Germann,Günter, AU - Roth,Christian, AU - Engel,Holger, PY - 2019/12/5/pubmed PY - 2019/12/5/medline PY - 2019/12/5/entrez SP - 106 EP - 112 JF - Annals of plastic surgery JO - Ann Plast Surg VL - 84 IS - 1 N2 - BACKGROUND: The mechanisms influencing the balance of nitric oxide (NO) bioavailability in tissues are negatively affected under diabetic and also under ischemic conditions. Free tissue transplantation for diabetic patients has to deal with both ischemic and diabetic circumstances, which lead to a significantly decrease in providing NO, thus increasing ischemia-reperfusion injury. In previous studies, we could prove that enhancing NO bioavailability leads to attenuated ischemia-reperfusion injury macrocirculatory and microcirculatory alterations in healthy and also in diabetes type 2 rats. This study is evaluating the role of inducible nitric oxide synthase in different dosages and L-arginine under diabetes type 1 conditions. METHODS: Diabetic type 1 conditions were established via streptozotocin over a period of 4 weeks and verified via blood sugar, insulin, and C-peptide levels. Vascular pedicle isolated rat skin flap model that underwent 3 hours of ischemia was used. At 30 minutes before ischemia, normal saline, inducible nitric oxide synthase (NOS) (1/2 IE), and L-arginine (50 mg/kg body weight) were administered systemically. Ischemia/reperfusion (I/R)-induced alterations were measured 5 days after the operation. RESULTS: The inducible NOS (iNOS) attenuated I/R-induced alterations under diabetic type 1 conditions significantly with vitality rates of 16.1% compared with control group (5.5%). Best results could be achieved with the combination of iNOS (1 IE) and L-arginine displaying vitality rates of 43%. Increased dosage of inducible nitric oxide (2 IE) led to decreased vitality rates (22.2%/27.4% without/with L-arginine). CONCLUSIONS: Supporting the mechanisms of NO bioavailability via exogenous application of iNOS and L-arginine significantly attenuated I/R-induced alterations in a skin flap rat model. This pharmacologic preconditioning could be an easy and effective interventional strategy to uphold conversation of L-arginine to NO even on ischemic and type 1 diabetic conditions. SN - 1536-3708 UR - https://www.unboundmedicine.com/medline/citation/31800556/Inducible_Nitric_Oxide_Synthase_and_L-Arginine_Optimizes_Nitric_Oxide_Bioavailability_in_Ischemic_Tissues_Under_Diabetes_Mellitus_Type_1 L2 - http://dx.doi.org/10.1097/SAP.0000000000002121 DB - PRIME DP - Unbound Medicine ER -