title: Antidepressant-induced inhibition of genital vascular responses is reversed by vardenafil in female rabbits.
abstract: 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.
authors.affiliation: 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.
authors.forename: Javier
authors.initials: J
authors.lastname: Angulo
authors.affiliation: Departamento de Investigación, Hospital Ramón y Cajal, Madrid, Spain.
authors.forename: Pedro
authors.initials: P
authors.lastname: Cuevas
authors.affiliation: Departamento de Investigación, Hospital Ramón y Cajal, Madrid, Spain.
authors.forename: Begona
authors.initials: B
authors.lastname: Cuevas
authors.affiliation: Bayer HealthCare, Wuppertal, Germany.
authors.forename: Erwin
authors.initials: E
authors.lastname: Bischoff
authors.affiliation: Instituto de Medicina Sexual, Fundación para la Investigación y el Desarollo en Andrología, Madrid,; Departamento de Investigación, Hospital Ramón y Cajal, Madrid, Spain.
authors.forename: Iñigo Saenz
authors.initials: IS
authors.lastname: De Tejada
mesh_terms: 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*
chemical_list: D000928:Antidepressive Agents; D007093:Imidazoles; D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D013450:Sulfones; D014227:Triazines; D014665:Vasodilator Agents; D000069058:Vardenafil Dihydrochloride