Nicorandil is an orally available drug that can act as a nitric oxide donor, an antioxidant, and an ATP-dependent K channel activator. We hypothesized that it may have a beneficial role in treating diabetic nephropathy. We administered nicorandil to a model of advanced diabetic nephropathy (the streptozotocin-induced diabetes in mice lacking endothelial nitric oxide synthase, eNOS KO); controls included diabetic eNOS KO mice without nicorandil, and nondiabetic eNOS KO mice treated with either nicorandil or vehicle. Mice were treated for 8 weeks. Histology, blood pressure and renal function determined. Additional studies involved examining the effects of nicorandil on cultured human podocytes. Here we found that nicorandil did not affect blood glucose levels, blood pressure or systemic endothelial function, but significantly reduced proteinuria, glomerular injury (mesangiolysis and glomerulosclerosis), and interstitial fibrosis. Nicorandil protected against podocyte loss and podocyte oxidative stress. Studies in cultured podocytes showed that nicorandil likely protects against glucose-mediated oxidant stress via the ATP dependent K channel as opposed to its NO stimulating effects. In conclusion, nicorandil may be beneficial in diabetic nephropathy by preserving podocyte function. We recommend clinical trials to determine if nicorandil may benefit diabetic nephropathy, or other conditions associated with podocyte dysfunction.
- endothelial dysfunction
- diabetic nephropathy
- Copyright © 2011, American Journal of Physiology - Renal Physiology