Erectile dysfunction in a murine model of sleep apnea.
BACKGROUND
Erectile dysfunction (ED) is frequent in obstructive sleep apnea syndrome (OSAS). Chronic intermittent hypoxia (CIH), one of the hallmarks of OSAS, could mediate ED.


OBJECTIVE
To determine whether intermittent hypoxia during sleep affects erectile dysfunction in mice.


METHODS
Three groups of C57BL/6 mice were exposed to CIH for 5 or 24 weeks. Sexual function was evaluated by in vivo telemetry of corpus spongiosum pressure. Spontaneous erections, sexual activity during mating, and noncontact tests were assessed after 5 weeks of CIH and after treatment with tadalafil. Plasma testosterone was measured after 8 and 24 weeks of CIH, and the expression of nitric oxide synthase (NOS) isoforms was examined in penile tissue.


RESULTS
Noncontact, spontaneous, and contact sexual activity in the mice was suppressed after CIH. Spontaneous erection counts decreased after the first week of CIH by 55% (P < 0.001) and remained unchanged thereafter. Recovery of erectile activity during normoxia for 6 weeks was incomplete. Compared with control mice, latencies for mounts and intromissions increased by 60- and 40-fold, respectively (P < 0.001), and the sexual activity index decreased sixfold. Tadalafil treatment significantly attenuated these effects. Immunoblot analyses of NOS proteins in the erectile tissue showed decreased expression of endothelial NOS after CIH (P < 0.01), with no changes in plasma testosterone levels after 8 and 24 weeks of CIH.


CONCLUSIONS
CIH during sleep is associated with decreased libido in mice. The decreased expression of endothelial NOS protein in erectile tissue and the favorable response to tadalafil suggest that altered nitric oxide mechanisms underlie CIH-mediated ED. No changes in testosterone emerge after intermittent hypoxia.
Kosair Children's Hospital Research Institute, University of Louisville, Department of Pediatrics, University of Louisville, Louisville, KY 40202, USA.
Galia K
GK
Soukhova-O'Hare
Zahoor A
ZA
Shah
Zhenmin
Z
Lei
Alexander D
AD
Nozdrachev
C Venkateswara
CV
Rao
David
D
Gozal
D000818:Animals; D015153:Blotting, Western; D002243:Carbolines / Q000627:therapeutic use; D015897:Comorbidity; D004195:Disease Models, Animal; D007172:Erectile Dysfunction / Q000097:blood / Q000453:epidemiology*; D004958:Estradiol / Q000097:blood; D000860:Hypoxia / Q000453:epidemiology*; D007150:Immunohistochemistry; D007989:Libido / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019001:Nitric Oxide Synthase / Q000378:metabolism; D010413:Penis / Q000378:metabolism; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use; D020181:Sleep Apnea, Obstructive / Q000453:epidemiology*; D000068581:Tadalafil; D013739:Testosterone / Q000097:blood
D002243:Carbolines; D010726:Phosphodiesterase Inhibitors; D013739:Testosterone; D004958:Estradiol; D000068581:Tadalafil; D019001:Nitric Oxide Synthase