Erectile dysfunction (ED) affects approximately half of men during middle age. Erectile
dysfunction is often an early symptom of systemic vascular disease, which may precipitate significant
cardiac events. The pathophysiology of ED and cardiovascular disease is closely linked. Endothelial
dysfunction occurs at an early stage in ED and cardiovascular disease (CVD). In normal conditions,
nitric oxide dependent and independent mechanisms regulate penile vascular tone ensuring an appropriate
balance of vasoconstriction and vasodilatation. A normal endothelium is responsible for mediating
the effect of pro-erectile mediators derived from the endothelium and is critical in normal erectile
function. Endothelial dysfunction disrupts the homeostatic mechanisms responsible for regulation of
smooth muscle contraction and penile vascular tone. Reduced bioavailability of nitric oxide (NO) occurs as a response to
endothelial damage. Phosphodiesterases further degrade levels of cyclic guanosine monophosphate (cGMP) and impair
smooth muscle relaxation and erectile function. A number of endothelium derived NO independent mediators of erectile
function have been described and are known to contribute to ED in the presence of endothelial damage. This review
provides an up to date analysis of the role of the endothelium in ED describing the pathways involved and how these
represent current and potential therapeutic targets.
Keywords: Erectile dysfunction, endothelium, nitric oxide, endothelin, rho kinase, asymmetric dimethylarginine.
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