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

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‐KO(T) (ie2)) were generated by crossing Arg1 (fl/fl) (controls) with Tie2Cre (tg/−) 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‐KO(T) (ie2) mice. Depletion of circulating arginine by intravenous infusion of arginase 1 or inhibition of nitric oxide synthase activity with L‐N(G)‐nitro‐arginine methyl ester increased mean arterial pressure similarly in control (9 ± 2 and 34 ± 2 mmHg, respectively) and Arg1‐KO(T) (ie2) mice (11 ± 3 and 38 ± 4 mmHg, respectively). Vasomotor responses were studied in isolated saphenous arteries of 12‐ and 34‐week‐old Arg1‐KO(T) (ie2) and control animals by wire myography. Diabetes was induced in 10‐week‐old control and Arg1‐KO(T) (ie2) 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‐KO(T) (ie2) 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.