Antidepressant-induced inhibition of genital vascular responses is reversed by vardenafil in female rabbits.
BACKGROUND
Administration of serotonin reuptake inhibitors (SRI) or serotonin and norepinephrine reuptake inhibitors (SNRI) relieves depressive symptoms but may cause sexual dysfunction in women and men.


OBJECTIVE
The aim of the present study was to evaluate the effects of the phosphodiesterase type 5 (PDE5) inhibitor, vardenafil, on inhibition of genital vascular responses (GVR) induced by SRI or SNRI administration in female rabbits.


METHODS
Vaginal and clitoral vasodilatory responses to pelvic nerve electrical stimulation were measured by laser Doppler flow needle probes.


RESULTS
GVR were significantly potentiated by vardenafil even at the low dose of 0.1 mg/kg, in clitoris and vagina (181 +/- 22% and 180 +/- 31% of control, in vagina and clitoris, respectively, at 8 Hz). The selective SRI, paroxetine (5 mg/kg), significantly inhibited GVR in female rabbits (54 +/- 5% and 48 +/- 6% of control). GVR were also significantly inhibited by the SNRIs, venlafaxine (5 mg/kg) (57 +/- 3% and 32 +/- 11%) and duloxetine (1 mg/kg) (40 +/- 7% and 28 +/- 5%). Treatment with vardenafil (0.1 and 0.3 mg/kg) completely reversed the inhibition of GVR induced by paroxetine, venlafaxine, or duloxetine.


CONCLUSIONS
Potentiation of the nitric oxide (NO) pathway by vardenafil improves vascular sexual responses in female rabbits and overcomes the inhibitory effects of acutely administered antidepressants on GVR, irrespective of the underlying pathophysiologic mechanism, i.e., disruption of the NO pathway or enhancement of alpha-adrenergic mechanisms. PDE5 inhibition may represent a reasonable approach to treat SRI- or SRNI-induced female sexual dysfunction, in particular, arousal disorders.
Angulo
Javier
J
Instituto de Medicina Sexual, Fundación para la Investigación y el Desarollo en Andrología, Madrid,; Departamento de Investigación, Hospital Ramón y Cajal, Madrid, Spain,. Electronic address: jangulo@ibercom.com.
Cuevas
Pedro
P
Departamento de Investigación, Hospital Ramón y Cajal, Madrid, Spain.
Cuevas
Begona
B
Departamento de Investigación, Hospital Ramón y Cajal, Madrid, Spain.
Bischoff
Erwin
E
Bayer HealthCare, Wuppertal, Germany.
De Tejada
Iñigo Saenz
IS
Instituto de Medicina Sexual, Fundación para la Investigación y el Desarollo en Andrología, Madrid,; Departamento de Investigación, Hospital Ramón y Cajal, Madrid, Spain.
D000818:Animals; D000928:Antidepressive Agents / Q000009:adverse effects; D001808:Blood Vessels / Q000187:drug effects; D004558:Electric Stimulation; D005260:Female; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D017078:Laser-Doppler Flowmetry; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology*; D011817:Rabbits; D012039:Regional Blood Flow / Q000187:drug effects; D012735:Sexual Dysfunction, Physiological / Q000188:drug therapy* / Q000209:etiology; D013450:Sulfones / Q000008:administration & dosage / Q000494:pharmacology; D014227:Triazines / Q000008:administration & dosage / Q000494:pharmacology; D014621:Vagina / Q000098:blood supply / Q000187:drug effects*; D000069058:Vardenafil Dihydrochloride; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*
D000928:Antidepressive Agents; D007093:Imidazoles; D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D013450:Sulfones; D014227:Triazines; D014665:Vasodilator Agents; D000069058:Vardenafil Dihydrochloride