heme-arginate and Metabolic-Syndrome

This translational randomized and vehicle-controlled cross-over study was performed to assess the impact of haem arginate treatment on haem oxygenase-1 induction, endothelial function and insulin sensitivity in subjects with the metabolic syndrome (n = 14). Both treatment periods consisted of 5 days. Haem arginate or vehicle (l-arginine) was administered intravenously on Days 1 and 3. Forearm blood flow in response to acetylcholine and nitroglycerine was measured by venous occlusion plethysmography (Day 3), insulin sensitivity by a hyperinsulinaemic clamp procedure (Day 5). Haem arginate did not improve endothelial function or insulin sensitivity but significantly reduced the vasodilator response to nitroglycerine (p < 0.01). These negative findings are in contrast to the preclinical data, which may be due to short duration of therapy and limited haem oxygenase-1 induction as well as interference by markedly elevated plasma haem levels observed after haem arginate treatment (p < 0.01). Future studies should pay attention to the delicate balance between sufficient dosing and timely normalization of plasma haem levels.

Topics: Acetylcholine; Adult; Aged; Arginine; Bilirubin; Cross-Over Studies; Endothelium, Vascular; Female; Ferritins; Glucose Clamp Technique; Heme; Heme Oxygenase-1; Humans; Insulin Resistance; Male; Metabolic Syndrome; Middle Aged; Nitroglycerin; Random Allocation; RNA, Messenger; Translational Research, Biomedical; Vasodilation; Vasodilator Agents