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.