This study tested the hypothesis that red blood cell (RBC) arginase represents a potential therapeutic target in ischemia-reperfusion in type 2 diabetes. Post-ischemic cardiac recovery was impaired in hearts from db/db mice compared with wild-type hearts. RBCs from mice and patients with type 2 diabetes attenuated post-ischemic cardiac recovery of nondiabetic hearts. This impaired cardiac recovery was reversed by inhibition of RBCs arginase or nitric oxide synthase. The results suggest that RBCs from type 2 diabetics impair cardiac tolerance to ischemia-reperfusion via a pathway involving arginase activity and nitric oxide synthase-dependent oxidative stress.
Keywords: ABH, 2 (S)-amino-6-boronohexanoic acid; KH, Krebs-Henseleit; L-NAME, NG-nitro-L-arginine methyl ester; LVDP, left ventricular developed pressure; LVEDP, left ventricular end-diastolic pressure; NAC, N-acetylcysteine; NO, nitric oxide; NOS, nitric oxide synthase; RBC, red blood cell; ROS, reactive oxygen species; WT, wild type; arginase; dP/dt, the first derivative of left ventricular pressure; eNOS, endothelial nitric oxide synthase; iNOS, inducible isoform of nitric oxide synthase; nitric oxide synthase; nor-NOHA, Nω-hydroxy-nor-L-arginine; reactive oxygen species; red blood cells; type 2 diabetes.