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Physiol Rep. 2018 Jun;6(11):e13717. doi: 10.14814/phy2.13717.

Deletion of endothelial arginase 1 does not improve vasomotor function in diabetic mice.

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Departments of Anatomy & Embryology, Maastricht University, Maastricht, the Netherlands.
Department of Pharmacology & Toxicology, Maastricht University, Maastricht, the Netherlands.
Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, the Netherlands.
Nutrim - School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, the Netherlands.
Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland.
Tytgat Institute for Liver & Intestinal Research, Academic Medical Center, Amsterdam, the Netherlands.
Department of Cardiovascular and Renal Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark.
Department of Cardiac, Thoracic and Vascular Surgery, Odense University Hospital, Odense, Denmark.


Endothelial arginase 1 was ablated to assess whether this prevents hyperglycemia-induced endothelial dysfunction by improving arginine availability for nitric oxide production. Endothelial Arg1-deficient mice (Arg1-KOTie2 ) were generated by crossing Arg1fl/fl (controls) with Tie2Cretg/- mice and analyzed by immunohistochemistry, measurements of hemodynamics, and wire myography. Ablation was confirmed by immunohistochemistry. Mean arterial blood pressure was similar in conscious male control and Arg1-KOTie2 mice. Depletion of circulating arginine by intravenous infusion of arginase 1 or inhibition of nitric oxide synthase activity with L-NG -nitro-arginine methyl ester increased mean arterial pressure similarly in control (9 ± 2 and 34 ± 2 mmHg, respectively) and Arg1-KOTie2 mice (11 ± 3 and 38 ± 4 mmHg, respectively). Vasomotor responses were studied in isolated saphenous arteries of 12- and 34-week-old Arg1-KOTie2 and control animals by wire myography. Diabetes was induced in 10-week-old control and Arg1-KOTie2 mice with streptozotocin, and vasomotor responses were studied 10 weeks later. Optimal arterial diameter, contractile responses to phenylephrine, and relaxing responses to acetylcholine and sodium nitroprusside were similar in normoglycemic control and Arg1-KOTie2 mice. The relaxing response to acetylcholine was dependent on the availability of extracellular l-arginine. In the diabetic mice, arterial relaxation responses to endothelium-dependent hyperpolarization and to exogenous nitric oxide were impaired. The data show that endothelial ablation of arginase 1 in mice does not markedly modify smooth muscle and endothelial functions of a resistance artery under normo- and hyperglycemic conditions.


Arginase 1 deficiency; endothelial dysfunction; nitric oxide

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