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This Article Full Text Full Text (PDF) All Versions of this Article: jpet.103.063362v1 310/1/141    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Angulo, J. Articles by de Tejada, I. S. Search for Related Content PubMed PubMed Citation Articles by Angulo, J. Articles by de Tejada, I. S. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB (L)-ARGININE CITALOPRAM HYDROBROMIDE CYCLOHEXANOL NITRIC OXIDE PHENTOLAMINE THIOPHENE VENLAFAXINE HYDROCHLORIDE Medline Plus Health Information Antidepressants

CARDIOVASCULAR

Mechanisms for the Inhibition of Genital Vascular Responses by Antidepressants in a Female Rabbit Model

Fundación para la Investigación y el Desarrollo en Andrología, Madrid, Spain (J.A., I.S.d.T.); Departamento de Investigación, Hospital Ramón y Cajal, Madrid, Spain (P.C., B.C.); and Department of Pharmacology and Toxicology, Forest Research Institute, Jersey City, New Jersey (S.G.)

Vaginal and clitoral vasodilator responses (genital vascular responses; GVRs) to pelvic nerve electrical stimulation in female rabbits were measured by laser Doppler flow needle probes. The intravenous administration of various treatments was evaluated. GVRs were attenuated by a nitric-oxide synthase inhibitor (48.5 and 51.8% of control at 8 Hz in the vagina and clitoris, respectively) and norepinephrine (NE) (78.5 and 61.5%), whereas serotonin (5-HT) had no inhibitory effect. The selective 5-HT reuptake inhibitor (SSRI) escitalopram did not modify GVRs, whereas the SSRI paroxetine dose-dependently inhibited GVRs in female rabbits (43.3 and 53.1% at 5 mg/kg). GVRs were also significantly inhibited by the 5-HT and NE reuptake inhibitors venlafaxine (53.4 and 52.6% at 5 mg/kg) and duloxetine (40.9 and 37.4% at 1 mg/kg). L-arginine prevented the inhibitory effects of paroxetine (105.5 and 115.3%) and partially prevented duloxetine-induced reduction of GVRs but had no effect on the inhibition of GVRs induced by venlafaxine. Conversely, the -adrenergic receptor blocker phentolamine had no effect on paroxetine-induced reduction of GVRs, partially prevented the inhibitory effects of duloxetine, and fully prevented the effects of venlafaxine (93.0 and 96.7%). Duloxetine-induced inhibition of GVRs was completely prevented by combined administration of L-arginine and phentolamine (123.5 and 103.6%). Although 5-HT or the highly selective SRI escitalopram did not inhibit GVRs, NE or inhibition of nitric oxide (NO) synthesis did. Inhibition of the NO pathway by paroxetine and duloxetine or activation of -adrenergic mechanisms by venlafaxine and duloxetine lead to antidepressant-induced inhibition of GVRs in female rabbits.

Address correspondence to: Dr. Iñigo Sáenz de Tejada, Antonio Robles, 4-9C, 28034 Madrid, Spain. E-mail: isdtejada{at}terra.es