Diabetes-mediated middle cerebral artery remodeling is restored by linagliptin: Interaction with the vascular smooth muscle cell endothelin system

摘要: Abstract Introduction Endothelin-1 (ET-1) mediates cerebrovascular remodeling in vascular smooth muscle layer of the middle cerebral arteries (MCA) type-2 diabetic Goto-Kakizaki (GK) rats. While metformin, oral glucose lowering agent, prevent/restores and reduce systemic local ET-1 levels whether this effect was specific to metformin remained unknown. Our working hypotheses were 1) linagliptin, a DPP-IV inhibitor, can reverse diabetes-mediated is associated with decreased ET-1, 2) linagliptin prevents high induced increase ET receptors brain cells (bVSMCs). Methods Diabetic non-diabetic GK rats treated (4 weeks). MCAs fixed buffered 4% paraformaldehyde used for morphometry. Human bVSMCs incubated normal (5.5 mM)/high (25 mM) conditions (100 nM; 24 h). secretion measured media cell lysate respectively. Immunostaining performed ET-A ET-B receptor. also (100 nM) linagliptin. Results Linagliptin treatment regressed animals but had no on blood glucose. normal/high condition did not show any significant difference or receptor expression. significantly increased inhibited by Conclusions effective reversing established pathological diabetes. Attenuation system could be pleiotropic that provides protection.