NADPH oxidase activation: a mechanism of erectile dysfunction in a rat model of sleep apnea.
Erectile dysfunction (ED) is a frequent occurrence in male patients with  obstructive sleep apnea syndrome (OSAS). Long-term intermittent hypoxia  (LTIH), one of the hallmarks of OSAS, could mediate ED. The objective of this  study was to test the hypothesis that increased nicotinamide adenine  dinucleotide phosphate (NADPH) oxidase activity contributes to ED in rat  responses to LTIH. Healthy male Sprague-Dawley rats were randomly distributed  into 4 groups: a LTIH group, an apocynin (a selective NADPH oxidase  inhibitor)-treated LTIH group, a sham LTIH group, and an apocynin-treated sham  group. Erectile function was examined by measuring the mean arterial blood  pressure (MAP) and intracavernosal pressure (ICP) on electrical stimulation of  the cavernous nerve. Real-time quantitative polymerase chain reaction and  Western blot were used to examine mRNA and protein expression of NADPH oxidase  subunit in corpus cavernosa (CC). The level of malondialdehyde and superoxide  dismutase were detected by colorimetry. Nitric oxide synthase (NOS) isoforms  in CC were also investigated. LTIH markedly attenuated the erectile responses  (ICP/MAP), and these were partially prevented by apocynin treatment. Promoted  oxidative stress-associated NADPH oxidase subunit activation was found  in CC from LTIH rats. Decreased expression and activity of constitutive NOS  (cNOS), including endothelial NOS and neuronal NOS, associated with enhanced  inducible NOS (iNOS) expression and activity were observed in LTIH rats.  Apocynin prevented the decrease in cNOS activity and inhibited iNOS expression  and activity in LTIH rats. These results indicate that NADPH oxidase  activation plays an important role in the pathogenesis of LTIH-mediated  ED.
Departments of Respiratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. liuhuiguo1966@yahoo.cn
Kui
K
Liu
Xian-Sheng
XS
Liu
Li
L
Xiao
Jin
J
Shang
Ming-Chao
MC
Li
Yong-Jian
YJ
Xu
Hui-Guo
HG
Liu
D000098:Acetophenones / Q000494:pharmacology*; D000818:Animals; D007172:Erectile Dysfunction / Q000209:etiology / Q000503:physiopathology*; D008297:Male; D019255:NADPH Oxidases / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010413:Penis / Q000503:physiopathology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D020181:Sleep Apnea, Obstructive / Q000503:physiopathology*
D000098:Acetophenones; C056165:acetovanillone; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D019255:NADPH Oxidases