Lymphatic vascular integrity is disrupted in type 2 diabetes due to impaired nitric oxide signalling

摘要: Aims Lymphatic vessel dysfunction is an emerging component of metabolic diseases and can lead to tissue lipid accumulation, dyslipidaemia, oedema. While lymph leakage has been implicated in obesity hypercholesterolaemia, whether similar lymphatic exists diabetes not investigated. Methods results To measure the integrity transgenic mice, we developed a new assay that quantifies solute permeability murine collecting vessels. Compared with age-matched wild-type (WT) controls, lymphatics from diabetic, leptin receptor-deficient ( db/db ) mice was elevated >130-fold. Augmenting nitric oxide (NO) production by suffusion l-arginine rescued this defect. Using pharmacological tools eNOS−/− found NO increased WT permeability, but reduced permeability. These conflicting actions were reconciled finding phosphodiesterase 3 (PDE3), normally inhibited signalling, active inhibition enzyme restored barrier function. Conclusion In conclusion, identified first vascular defect type 2 diabetes, enhanced caused low bioavailability. Further, demonstrates PDE3 required maintain represents viable therapeutic target for endothelial disease.