Chronic escitalopram treatment induces erectile dysfunction by decreasing nitric oxide bioavailability mediated by increased nicotinamide adenine dinucleotide phosphate oxidase activity and reactive oxygen species production.
OBJECTIVE
To investigate the effects of escitalopram, a selective serotonin reuptake inhibitor, on erectile and penile vascular function in the rat.


METHODS
The effect of chronic treatment with escitalopram (0.286 mg/kg/day) on change in intracavernosal pressure, maximum intracavernosal pressure/mean arterial pressure, and area under the intracavernosal pressure curve in response to cavernosal nerve stimulation was measured. The effect of chronic escitalopram treatment on endothelial-dependent relaxant responses was investigated in isolated mesenteric and internal pudendal resistance arteries. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity and nitric oxide synthase levels were determined with enzymatic assay and Western blot, respectively.


RESULTS
Chronic treatment with escitalopram resulted in a significant reduction in the erectile response to cavernosal nerve stimulation without an effect on the response to intracavernosal injection of the nitric oxide donor sodium nitroprusside. The decrease in erectile function was associated with marked increases in NADPH oxidase activity in the corpora cavernosa. Treatment with escitalopram also caused a significant reduction in the relaxant response to acetylcholine in isolated internal pudendal and mesenteric resistance arteries without altering the response to sodium nitroprusside. The decreased response to acetylcholine in the isolated vascular segments was associated with a marked increase in NADPH oxidase activity that was corrected by treatment with the NAPDH oxidase inhibitor apocynin.


CONCLUSIONS
The inhibitory effects of escitalopram on erectile and vascular function were not accompanied by a change in endothelial nitric oxide synthase, neuronal nitric oxide synthase, inducible nitric oxide synthase expression, or endothelial nitric oxide synthase activity, suggesting that the inhibitory effect is caused by a decrease in nitric oxide bioavailability mediated by increased NADPH oxidase and reactive oxygen species production.
Department of Physiology, Tulane University School of Medicine, New Orleans, LA.
Modar
M
Kassan
George F
GF
Lasker
Suresh C
SC
Sikka
Sree Harsha
SH
Mandava
Ahmet
A
Gokce
Khalid
K
Matrougui
Wayne J G
WJ
Hellstrom
Philip J
PJ
Kadowitz
Ege Can
EC
Serefoglu
D000098:Acetophenones / Q000737:chemistry; D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D015283:Citalopram / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects; D007172:Erectile Dysfunction / Q000139:chemically induced*; D008297:Male; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D018384:Oxidative Stress; D010410:Penile Erection / Q000187:drug effects*; D010413:Penis / Q000187:drug effects*; D010766:Phosphorylation; D051381:Rats; D011921:Rats, Inbred WKY; D017382:Reactive Oxygen Species / Q000378:metabolism; D016896:Treatment Outcome
D000098:Acetophenones; D017382:Reactive Oxygen Species; D015283:Citalopram; D009569:Nitric Oxide; C056165:acetovanillone; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D019255:NADPH Oxidases; D000109:Acetylcholine