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Erectile DysfunctionErectile Dysfunction
Normal erectile function involves 3Normal erectile function involves 3
synergistic and simultaneoussynergistic and simultaneous
processes:processes: 1) neurologically mediated increase in1) neurologically mediated increase in
penile arterial inflowpenile arterial inflow
2) relaxation of2) relaxation of cavernosalcavernosal smoothsmoothmusclemuscle
3) restriction of venous outflow from the3) restriction of venous outflow from the
penispenis
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Erectile dysfunctionErectile dysfunction ED is predominately a disease ofED is predominately a disease of
vascular origin.vascular origin.
The incidence ofED dramaticallyThe incidence ofED dramatically
increases in men with diabetesincreases in men with diabetesmellitus, hypercholesterolemia, andmellitus, hypercholesterolemia, and
cardiovascular disease.cardiovascular disease.
Loss of the functional integrity of theLoss of the functional integrity of theendothelium and subsequentendothelium and subsequent
endothelial dysfunction plays anendothelial dysfunction plays an
integral role in the occurrence ofED inintegral role in the occurrence ofED in
this cohort of men.this cohort of men.
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Erectile dysfunctionErectile dysfunction
The corpusThe corpus cavernosumcavernosum of the penisof the penisis composed of a meshwork ofis composed of a meshwork of
interconnected smooth muscle cellsinterconnected smooth muscle cellslined by vascular endothelium.lined by vascular endothelium.
Endothelial cells and underlyingEndothelial cells and underlyingsmooth muscle also line the smallsmooth muscle also line the small
resistanceresistance helicinehelicine arteries thatarteries thatsupply blood to the corpussupply blood to the corpuscavernosumcavernosum during penileduring peniletumescence.tumescence.
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Role of Endothelium in ErectionsRole of Endothelium in Erections
NO production from nNOS in theNO production from nNOS in the
NANC nerves innervating the penis isNANC nerves innervating the penis is
essential for the initiation ofessential for the initiation ofcavernosal smooth muscle relaxationcavernosal smooth muscle relaxation
and subsequent erectionand subsequent erection
The relative importance of endothelialThe relative importance of endothelial--derived NO from eNOS in thederived NO from eNOS in the
endothelial cells of the corpusendothelial cells of the corpus
cavernosum and arteries supplyingcavernosum and arteries supplying
the enis has recentl been elucidatedthe enis has recentl been elucidated
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Role of Endothelium inRole of Endothelium in
ErectionErection NO diffuses to adjacent smoothNO diffuses to adjacent smooth
muscle cells stimulatingmuscle cells stimulating guanylateguanylate
cyclasecyclase. This interaction converts. This interaction convertsguanosineguanosine triphosphatetriphosphate (GTP) to(GTP) to
cycliccyclic guanosineguanosine monophosphatemonophosphate
((cGMPcGMP), which induces a substantial), which induces a substantialincrease in intracellularincrease in intracellular cGMPcGMP,,
causing smooth muscle relaxationcausing smooth muscle relaxation
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Role of EndotheliumRole of Endothelium
The vascular endothelium not only servesThe vascular endothelium not only serves
as a passive barrier for the arterial andas a passive barrier for the arterial and
venous blood, but also plays a pivotal rolevenous blood, but also plays a pivotal role
in modulating vascular tone and blood flowin modulating vascular tone and blood flow
in response toin response to humoralhumoral, neural, and, neural, and
mechanical stimulimechanical stimuli
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ENDOTHELIAL DYSFUNCTION
Also seen in
Heart disease Hypertension
Diabetes mellitus
Metabolic syndrome
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ArteryArtery Size (mm)Size (mm) ClinicalClinical
Event
Event
PenilePenile 11--22 EDED
CoronaryCoronary 33--44 CADCADCarotidCarotid 55--77 TIA/StrokeTIA/Stroke
FemoralFemoral 66--88 ClaudicationClaudication
Artery size and Atherothrombosis
Montorsi et alEur Urol2003; 44:352-4
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ED and Cardiac PatientsED and Cardiac Patients
MMASMMAS men with cardiovascular disease,men with cardiovascular disease,
diabetes or hypertension 4 times thediabetes or hypertension 4 times the
incidence of complete EDincidence of complete ED
Myocardial infarction 44%Myocardial infarction 44%
Untreated hypertension 17%Untreated hypertension 17%
Treated hypertension 25%Treated hypertension 25%
ED increases with increasing CADED increases with increasing CAD
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Endothelial Dysfunction and Diabetes
Peripheral vascular disease and neuropathyPeripheral vascular disease and neuropathyof autonomic nerves are establishedof autonomic nerves are establishedcomplications associated with diabetescomplications associated with diabetes
mellitusmellitus Such alterations in the peripheralSuch alterations in the peripheral
vasculature may underlie the highvasculature may underlie the highprevalence (.50%) of diabetic ED in menprevalence (.50%) of diabetic ED in men
(Hakim and Goldstein, 1996)(Hakim and Goldstein, 1996)
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Oxidative stress
Endothelial
cell injury
Diabetes
Hypertension
Vasoconstriction
Erectile dysfunction Thrombosis
Atherosclerosis
Smoking
Dyslipidemia
Precursors
Outcomes
Endothelial Insults:Endothelial Insults:
The ED LinkThe ED Link
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The recognition ofED as a warning signThe recognition ofED as a warning sign
of silent vascular disease has led to theof silent vascular disease has led to the
concept that a man with ED and noconcept that a man with ED and no
cardiac symptoms is a cardiaccardiac symptoms is a cardiac
(or vascular) patient until proven(or vascular) patient until proven
otherwise.otherwise.
Princeton II: Jackson G et al. 2006.Princeton II: Jackson G et al. 2006. J Sex Med 3:28J Sex Med 3:28--3636
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Diagnosis of ED : Why is itDiagnosis of ED : Why is it
important?important?
ED often leads to
- Anxiety, depression, loss of self-esteem, and diminished quality of life
- Diminished willingness to initiate sexual relationships withdrawal from
intimate relationships
- Negative effect on their overall health
- Screening patients forED may actually uncover underlying factors
important to their patients' health
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