Aversa.2_EU Urological Review 15/03/2010 13:01 Page 78
Erectile Dysfunction
Endothelial Function and Erectile Dysfunction
Antonio Aversa, Roberto Bruzziches, Davide Francomano and Andrea Lenzi
Department of Medical Pathophysiology, University of Rome ‘La Sapienza’
Abstract
The vascular endothelium has an important role in modulating vascular tone and blood flow into the penis in response to humoral, neural and
mechanical stimuli. Endothelial dysfunction occurs in a variety of pathological conditions in internal medicine, but drugs that improve endothelial
function – antihypertensives, statins, antioxidants, etc. – are unable to improve erectile function since they lack specificity of action at the level
of the penile vasculature and smooth-muscle cells. Phosphodiesterase type-5 inhibitors (PDE5-i) are a class of drugs that have revolutionised
the treatment of male erectile dysfunction. A great debate regarding once-daily administration of PDE5-i for endothelial rehabilitation exists,
as it has been demonstrated that these drugs do not produce sustained clinical benefits in terms of erection above those observed with
on-demand administration beyond cessation of treatment. The aim of this article is to provide evidence-based data regarding the effect of PDE5-
i administration on endothelial function in patients in whom endothelial dysfunction is present.
Keywords
Endothelium, nitric oxide, phosphodiesterase type-5 inhibitors, sexual dysfunction, internal medicine
Disclosure: The authors have no conflicts of interest to declare.
Received: 11 December 2009 Accepted: 15 January 2010
Correspondence: Antonio Aversa, Dipartimento Fisiopatologia Medica, Sapienza University of Rome, Viale Policlinico 155, 00161 Rome, Italy.
antonio.aversa@uniroma1.it
Erectile dysfunction (ED) is defined as the consistent or recurrent previously unresponsive to on-demand regimes opens a new
inability of a man to attain and/or maintain a penile erection sufficient scenario in the treatment of men with ED and co-morbidities.
11,12
The
for sexual activity.
1
ED may constitute the first manifestation of aim of this article is to provide evidence-based data regarding
important systemic or relational pathologies and it is considered a the effect of PDE5-i administration on endothelial function in patients
possible marker of clinically undiagnosed disease, thus representing in whom endothelial dysfunction is present.
the ‘tip of the iceberg’ of a systemic vascular disorder.
2
It is common
(almost 50%) in men with diabetes and is often associated with Endothelial Function
vascular disease, such as coronary and peripheral atherosclerosis, The endothelium is the single layer of cells that line the luminal
and an increased risk of future cardiovascular events similar to that of surface of blood vessels. Over the past few years, it has become
men with coronary artery disease (CAD).
3,4
Therefore, regarding the increasingly apparent that it is far more than just a structural lining,
risk of cardiovascular events, diabetes can be considered equivalent and in fact has a range of important physiological functions. It acts as
to established CAD.
5
Ageing, obesity, cigarette smoking and the a direct interface between the components of circulating blood and
presence of diabetic complications (peripheral neuropathy, vascular local tissue and regulates numerous local blood vessel functions,
disease, retinopathy and nephropathy) show a significant relationship including vascular tone, cell adhesiveness, coagulation, inflammation
with the occurrence of ED in both type 1 and type 2 diabetes.
6
A large and permeability. Through these multiple functions, the endothelium
body of evidence has accumulated to suggest that the impairment is primarily responsible for enabling the arterial system to deliver
of vascular endothelial function is an initial step towards the sufficient tissue perfusion.
development of atherosclerosis. Endothelial function is impaired
in patients with overt atherosclerotic disease as well as in those with Endothelial cells have dichotomous functions in regulating the
increased cardiovascular risk factors (CRFs), and it is often present coagulation cascade. In a normal physiological state, healthy
in men with diabetes without clinically evident atherosclerotic endothelium serves as an anticoagulant membrane, exerting
diseases.
7,8
ED and CAD overlap in terms of CRFs, pathological basis predominantly fibrinolytic, anticoagulant and anti-aggregatory effects.
of disease and disease progression. The common underlying factor is These effects occur with the expression of antithrombin III (which
endothelial dysfunction (EDys). EDys, measured as impaired inhibits fibrinogen-to-fibrin conversion), heparin-like molecules (which
vasodilatation, is prognostic for cardiovascular events such as enhance antithrombin III activity) and tissue factor pathway inhibitor
myocardial ischaemia and stroke.
9,10
The recent discovery that chronic, (which inactivates the extrinsic pathway). They also secrete tissue-type
not on-demand administration of phosphodiesterase type-5 inhibitors plasminogen activator (tPA). Additionally, endothelial cells bind
(PDE5-i) may improve erectile and endothelial response in men thrombin, leading to protein C activation and, eventually, inactivation of
78 © TOUCH BRIEFINGS 2009
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