Differential effects of serotonin reuptake inhibitors on erectile responses, NO-production, and neuronal NO synthase expression in rat corpus cavernosum tissue.
Increased incidence of impotence is associated with some selective serotonin-reuptake-inhibitors (SSRIs), but the pathophysiological mechanism is unknown. Paroxetine and citalopram are extensively used SSRIs, but only paroxetine has been shown to inhibit nitric oxide synthase (NOS) activity. NO is a key mediator of penile erection. Thus, the aim of this study was to determine the effects of paroxetine and citalopram on erectile function and NO production, in a rat model. Application of cavernosal nerve electrical stimulation produced frequency-related intracavernosal pressure (ICP) increases, which were inhibited by the NOS inhibitor, N(G)-nitro-L-arginine (0.3 mg x kg(-1)). Acute or chronic (2 weeks) paroxetine-treatment (10 mg x kg(-1)) reduced ICP-responses, while citalopram did not. Paroxetine, but not citalopram, significantly reduced nitrite+nitrate plasma levels by 61.4% and inhibited penile neuronal NOS (nNOS) protein expression by 31.2% after chronic treatment. The results show that paroxetine inhibits erectile responses in rats. We propose that this effect is due to reduced NO production and nNOS expression.
Angulo
J
J
Fundación para la Investigación y el Desarrollo en Andrología, Department de Investigación, Hospital Ramón y Cajal, Madrid, Spain.
Peiró
C
C
Sanchez-Ferrer
C F
CF
Gabancho
S
S
Cuevas
P
P
Gupta
S
S
Sáenz de Tejada
I
I
D000818:Animals; D015283:Citalopram / Q000494:pharmacology / Q000627:therapeutic use; D004558:Electric Stimulation; D007172:Erectile Dysfunction / Q000188:drug therapy; D008297:Male; D009474:Neurons / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D017374:Paroxetine / Q000494:pharmacology / Q000627:therapeutic use; D010410:Penile Erection / Q000187:drug effects*; D010413:Penis / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use
D015283:Citalopram; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D017374:Paroxetine; D017367:Selective Serotonin Reuptake Inhibitors