title: Effects of acute administration of selective serotonin reuptake inhibitors on sympathetic nerve activity.
abstract: Serotonergic mechanisms have an important function in the central control of circulation. Here, the acute effects of three selective serotonin (5-HT) reuptake inhibitors (SSRIs) on autonomic and cardiorespiratory variables were measured in rats. Although SSRIs require 2-3 weeks to achieve their full antidepressant effects, it has been shown that they cause an immediate inhibition of 5-HT reuptake. Seventy male Wistar rats were anesthetized with urethane and instrumented to record blood pressure, heart rate, renal sympathetic nerve activity (RSNA), and respiratory frequency. At lower doses, the acute cardiovascular effects of fluoxetine, paroxetine and sertraline administered intravenously were insignificant and variable. At middle and higher doses, a general pattern was observed, with significant reductions in sympathetic nerve activity. At 10 min, fluoxetine (3 and 10 mg/kg) reduced RSNA by -33 ± 4.7 and -31 ± 5.4%, respectively, without changes in blood pressure; 3 and 10 mg/kg paroxetine reduced RSNA by -35 ± 5.4 and -31 ± 5.5%, respectively, with an increase in blood pressure +26.3 ± 2.5; 3 mg/kg sertraline reduced RSNA by -59.4 ± 8.6%, without changes in blood pressure. Sympathoinhibition began 5 min after injection and lasted approximately 30 min. For fluoxetine and sertraline, but not paroxetine, there was a reduction in heart rate that was nearly parallel to the sympathoinhibition. The effect of these drugs on the other variables was insignificant. In conclusion, acute peripheral administration of SSRIs caused early autonomic cardiovascular effects, particularly sympathoinhibition, as measured by RSNA. Although a peripheral action cannot be ruled out, such effects are presumably mostly central.
authors.affiliation: Departamento de Ciências Fisiológicas, Centro de Ciências da Saúde, Universidade Federal do Espírito Santo, Vitória, ES, Brasil.
authors.forename: R V
authors.initials: RV
authors.lastname: Tiradentes
authors.affiliation: Centro Universitário do Espírito Santo, Colatina, ES, Brasil.
authors.forename: J G P
authors.initials: JG
authors.lastname: Pires
authors.affiliation: Departamento de Morfologia, Centro de Ciências da Saúde, Universidade Federal do Espírito Santo, Vitória, ES, Brasil.
authors.forename: N F
authors.initials: NF
authors.lastname: Silva
authors.affiliation: Department of Neuroscience, Physiology and Pharmacology, University College London, London, UK.
authors.forename: A G
authors.initials: AG
authors.lastname: Ramage
authors.affiliation: Departamento de Ciências Fisiológicas, Centro de Ciências da Saúde, Universidade Federal do Espírito Santo, Vitória, ES, Brasil.
authors.forename: C H
authors.initials: CH
authors.lastname: Santuzzi
authors.affiliation: Escola de Medicina da Empresa Brasileira de Ensino, Vitória, ES, Brasil.
authors.forename: H A
authors.initials: HA
authors.lastname: Futuro Neto
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000494:pharmacology; D062186:Arterial Pressure / Q000187:drug effects; D017704:Baroreflex / Q000187:drug effects; D002320:Cardiovascular Physiological Phenomena / Q000187:drug effects; D005473:Fluoxetine / Q000008:administration & dosage* / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D007668:Kidney / Q000187:drug effects* / Q000294:innervation / Q000601:surgery; D008297:Male; D017374:Paroxetine / Q000008:administration & dosage* / Q000494:pharmacology; D017208:Rats, Wistar; D056152:Respiratory Rate / Q000187:drug effects; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology; D020280:Sertraline / Q000008:administration & dosage* / Q000494:pharmacology; D013564:Sympathetic Nervous System / Q000187:drug effects*; D055986:Vital Signs / Q000187:drug effects
chemical_list: D000928:Antidepressive Agents; D005473:Fluoxetine; D017374:Paroxetine; D017367:Selective Serotonin Reuptake Inhibitors; D020280:Sertraline