title: Effects of nitric oxide synthesis inhibitor or fluoxetine treatment on depression-like state and cardiovascular changes induced by chronic variable stress in rats.
abstract: Comorbidity between mood disorders and cardiovascular disease has been described extensively. However, available antidepressants can have cardiovascular side effects. Treatment with selective inhibitors of neuronal nitric oxide synthase (nNOS) induces antidepressant effects, but whether the antidepressant-like effects of these drugs are followed by cardiovascular changes has not been previously investigated. Here, we tested in male rats exposed to chronic variable stress (CVS) the hypothesis that nNOS blockers are advantageous compared with conventional antidepressants in terms of cardiovascular side effects. We compared the effects of chronic treatment with the preferential nNOS inhibitor 7-nitroindazole (7-NI) with those evoked by the conventional antidepressant fluoxetine on alterations that are considered as markers of depression (immobility in the forced swimming test, FST, decreased body weight gain and increased plasma corticosterone concentration) and cardiovascular changes caused by CVS. Rats were exposed to a 14-day CVS protocol, while being concurrently treated daily with either 7-NI (30 mg/kg) or fluoxetine (10 mg/kg). Fluoxetine and 7-NI prevented the increase in immobility in the FST induced by CVS and reduced plasma corticosterone concentration in stressed rats. Both these treatments also prevented the CVS-evoked reduction of the depressor response to vasodilator agents and baroreflex changes. Fluoxetine and 7-NI-induced cardiovascular changes independent of stress exposure, including cardiac autonomic imbalance, increased intrinsic heart rate and vascular sympathetic modulation, a reduction of the pressor response to vasoconstrictor agents, and impairment of baroreflex activity. Altogether, these findings provide evidence that fluoxetine and 7-NI have similar effects on the depression-like state induced by CVS and on cardiovascular function.
authors.affiliation: a Laboratory of Pharmacology , School of Pharmaceutical Sciences, São Paulo State University , UNESP, Araraquara, SP , Brazil and.|b Joint UFSCar-UNESP Graduate Program in Physiological Sciences , São Carlos, SP , Brazil.
authors.forename: Jeferson
authors.initials: J
authors.lastname: Almeida
authors.affiliation: a Laboratory of Pharmacology , School of Pharmaceutical Sciences, São Paulo State University , UNESP, Araraquara, SP , Brazil and.|b Joint UFSCar-UNESP Graduate Program in Physiological Sciences , São Carlos, SP , Brazil.
authors.forename: Josiane O
authors.initials: JO
authors.lastname: Duarte
authors.affiliation: a Laboratory of Pharmacology , School of Pharmaceutical Sciences, São Paulo State University , UNESP, Araraquara, SP , Brazil and.|b Joint UFSCar-UNESP Graduate Program in Physiological Sciences , São Carlos, SP , Brazil.
authors.forename: Leandro A
authors.initials: LA
authors.lastname: Oliveira
authors.affiliation: a Laboratory of Pharmacology , School of Pharmaceutical Sciences, São Paulo State University , UNESP, Araraquara, SP , Brazil and.|b Joint UFSCar-UNESP Graduate Program in Physiological Sciences , São Carlos, SP , Brazil.
authors.forename: Carlos C
authors.initials: CC
authors.lastname: Crestani
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001341:Autonomic Nervous System / Q000187:drug effects; D017704:Baroreflex / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects*; D002319:Cardiovascular System / Q000187:drug effects*; D002908:Chronic Disease; D003345:Corticosterone / Q000097:blood; D003863:Depression / Q000097:blood / Q000523:psychology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005473:Fluoxetine / Q000494:pharmacology*; D007191:Indazoles / Q000494:pharmacology*; D008297:Male; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar; D013315:Stress, Psychological / Q000097:blood / Q000523:psychology*; D013550:Swimming; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology; D015430:Weight Gain / Q000187:drug effects
chemical_list: D000928:Antidepressive Agents; D004791:Enzyme Inhibitors; D007191:Indazoles; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D005473:Fluoxetine; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat; C080122:7-nitroindazole; D003345:Corticosterone
keywords: Autonomic activity; baroreflex; forced swimming test; neuronal nitric oxide synthase; serotonin; unpredictable stress