Distinct mechanisms implicated in atherosclerosis-induced erectile dysfunction in rabbits.
Ageing and atherosclerosis (ATH) are well-known risk factors for erectile dysfunction (ED). To identify the mechanisms implicated in ATH-induced ED, independently of its ageing-associated component, we studied (i) erectile responses in vivo, and, (ii) endothelium-dependent and independent relaxations of corporal strips from young adult (YAD, n=6), adult (AD, n=6), and cholesterol-fed (ATH, n=8) New-Zealand white rabbits. Measurement of Intima/Media (I/M) ratio on iliac arteries from ATH rabbits determined those with moderate (Mod ATH, 0.5+/-0.3) or severe (Sev ATH, 1.5+/-0.4, P<0.05 Mann-Whitney) atherosclerotic lesions. Erectile responses were reduced in AD compared with YAD rabbits (at 6 V to 10 Hz: 51.6+/-4.6% vs. 57.5+/-1.4%); they were similar in AD and mod ATH rabbits (48.1+/-4.6%) but drastically impaired in Sev ATH rabbits (34.8+/-5.4%, P<0.05, two-way analysis of variance (ANOVA)). Corporal endothelium-dependent and -independent relaxations were comparable in YAD and AD rabbits (maximal relaxation to acetylcholine: 51.3+/-9.5 vs. 56.1+/-9.3%) but decreased in ATH rabbits (37.1+/-1.6%, P<0.001, two-way ANOVA). These results suggest that the mechanisms implicated in ATH-induced ED are distinct from the ageing-related process in rabbits. Thus, future therapeutic targets to treat or prevent ATH-induced ED may include the reduction of the atherosclerotic plaque size or progression, as well as an improvement of the smooth muscle and endothelial reactivity of the corpus cavernosum.
Behr-Roussel
Delphine
D
Pelvipharm, Domaine INRA, Route de la Guyonnerie, 91440, Bures sur Yvette, France.
Bernabe
Jacques
J
Compagnie
Sandrine
S
Rupin
Alain
A
Verbeuren
Tony J
TJ
Alexandre
Laurent
L
Giuliano
François
F
D000818:Animals; D001161:Arteriosclerosis / Q000150:complications*; D007172:Erectile Dysfunction / Q000209:etiology* / Q000503:physiopathology*; D006937:Hypercholesterolemia / Q000150:complications / Q000473:pathology; D008297:Male; D009126:Muscle Relaxation; D009130:Muscle, Smooth / Q000187:drug effects / Q000503:physiopathology; D010410:Penile Erection; D010413:Penis / Q000187:drug effects / Q000503:physiopathology; D010656:Phenylephrine / Q000494:pharmacology; D011817:Rabbits; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D014662:Vasoconstrictor Agents; D010656:Phenylephrine