Diabetic nephropathy: Treatment with phosphodiesterase type 5 inhibitors

Abstract

The importance of nitric oxide (NO) in vascular physiology is irrefutable; it stimulates the intracellular production of cyclic guanosine monophosphate (cGMP), initiating vascular smooth muscle relaxation. This biochemical process increases the diameter of small arteries, regulating blood flow distribution between arterioles and the microvasculature. The kidney is no exception, since NO predominantly dilates the glomerular afferent arterioles. It is now evident that the vascular production of cGMP can be augmented by inhibitors of phosphodiesterase type 5 (PDE 5), the enzyme which breakdowns this cyclic nucleotide. This has clinical relevance, since diabetic nephropathy (DN) a major microvascular complication of diabetes mellitus and the most common cause of end-stage renal disease, increases intraglomerular capillary pressure, leading to glomerular hypertension. PDE 5 inhibitors may have, therefore, the potential to reduce glomerular hypertension. This review describes the use of PDE 5 inhibitors to improve the metabolic, haemodynamic and inflammatory pathways/responses, all of which are dysfunctional in DN.

Keywords: Diabetic nephropathy, Phosphodiesterase type 5, Glomerular filtration rate, Inflammation, Angiotensin II

Core tip: Diabetic nephropathy a leading cause of end-stage renal disease, is characterized by dysfunctional metabolic, haemodynamic and inflammatory pathways leading to glomerular hypertension. These pathways were normalized following treatment with phosphodiesterase type 5 inhibitors, which initiated renal vascular smooth muscle relaxation. This therapeutic option for treating diabetic nephropathy may negate the need for costly renal dialysis or transplantation.