Antidepressant-Induced Inhibition of Genital Vascular Responses is Reversed by Vardenafil in Female Rabbits

Abstract

Introduction 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. Aim 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 α-adrenergic mechanisms. PDE5 inhibition may represent a reasonable approach to treat SRI- or SRNI-induced female sexual dysfunction, in particular, arousal disorders.

In vivo evaluation of vaginal films for mucosal delivery of nitric oxide

“…Although the treatment of FSAD has various options including hormone therapy, phosphodiesterase (PDE) inhibitors and alphablockers, mostly through enhancement of the vaginal blood flow [6,[8][9][10][11][12][13], they possess undesired side effects following their systemic administration. For examples, since PDE inhibitors and ablockers affected the systemic blood pressure and cardiac function, their clinical usages often resulted in adverse activities in cardiovascular regulation.…”

Sexual dysfunction in women: What can urologists contribute?

“…Angulo et al [30] examined the effects of PDE5 inhibition of genital vascular responses induced by serotonin reuptake inhibitors or serotonin and norepinephrine reuptake inhibitors. Vaginal and clitoral vasodilatory responses were measured to pelvic nerve electrical stimulation by laser Doppler fl ow needle probes.…”

“…Treatment with PDE5 inhibitor completely reversed the inhibition of genital vascular responses induced by paroxetine, venlafaxine, or duloxetine. They concluded that PDE5 inhibition may represent a reasonable approach to treat antidepressant-induced female sexual dysfunction, in particular, arousal disorders [30].…”

“…Replacement of genital tissues with sex steroids improves genital structure and function. Phosphodiesterase type 5 (PDE5) inhibitors [28][29][30] act on PDE5 enzymes present in female genital tissues and facilitate arousal responses.…”

Female Sexual Dysfunction: Therapeutic Options and Experimental Challenges

“…Intracavernous pressure and blood flow can be measured by inserting a probe into vaginal tissue and the corpus cavernosum, and signals to a laser Doppler blood flow monitor and thus, following PNS, changes in vaginal and clitoral blood flow can be measured. Recently, Angulo and colleagues demonstrated that treatment with vardenafil, a PDE5 inhibitor, increased vaginal and clitoral blood flow following PNS, which was assessed by laser Doppler, in a FSD-rabbit model where the animals were treated with anti-depressants [25]. The use of the female New Zealand white rabbit has given tremendous insight into genital hemodynamic measurements.…”