Fluoxetine Effect on Aortic Nitric Oxide-Dependent Vasorelaxation in the Unpredictable Chronic Mild Stress Model of Depression in Mice

Isingrini, Elsa; Belzung, Catherine; Freslon, Jean‐Louis; Machet, Marie‐Christine; Camus, Vincent

doi:10.1097/psy.0b013e31823a43e0

Cited by 38 publications

(40 citation statements)

References 44 publications

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“…Both fluoxetine and 7-NI prevented the CVS-induced reduction of the depressor response to acetylcholine and SNP. These data are consistent with the finding that chronic treatment with fluoxetine reverses CVS-evoked impairment in NO-dependent relaxation in aortic rings in vitro (Isingrini et al, 2012). Pharmacological treatment with either fluoxetine or 7-NI also decreased the pressor response to phenylephrine in unstressed rats.…”

Section: Discussionsupporting

confidence: 91%

Effects of nitric oxide synthesis inhibitor or fluoxetine treatment on depression-like state and cardiovascular changes induced by chronic variable stress in rats

Almeida

Duarte

Oliveira

et al. 2015

Stress

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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.

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Section: Discussionsupporting

confidence: 91%

Effects of nitric oxide synthesis inhibitor or fluoxetine treatment on depression-like state and cardiovascular changes induced by chronic variable stress in rats

Almeida

Duarte

Oliveira

et al. 2015

Stress

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“…We found, however, that escitalopram treatment significantly potentiated the EDH-like component of relaxation and that this effect was most pronounced in escitalopram responders. The observed changes are in contrast to a previous report showing that SSRI (fluoxetine) treatment in mice improves NO-dependent relaxation and suppresses EDH-like relaxation in the aorta (38). These contradictory findings could be a consequence of vessel size.…”

Section: Discussioncontrasting

confidence: 55%

Chronic selective serotonin reuptake inhibition modulates endothelial dysfunction and oxidative state in rat chronic mild stress model of depression

Matchkov

Кравцова

Wiborg

et al. 2015

American Journal of Physiology-Regulatory, Integrative and Comp

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Matchkov VV, Kravtsova VV, Wiborg O, Aalkjaer C, Bouzinova EV. Chronic selective serotonin reuptake inhibition modulates endothelial dysfunction and oxidative state in rat chronic mild stress model of depression. Am J Physiol Regul Integr Comp Physiol 309: R814 -R823, 2015. First published August 12, 2015 doi:10.1152/ajpregu.00337.2014.-Major depression is known to be associated with cardiovascular abnormalities, and oxidative stress has been suggested to play a role. We tested the hypothesis that antidepressant treatment reduces oxidative stress and endothelial dysfunctions in the chronic mild stress (CMS) model of depression in rats. Rats with Ͼ30% reduction in sucrose intake after 4 wk of CMS were defined in the study as CMS-susceptible and compared with unstressed controls. Sixteen CMS-susceptible and eight unstressed rats were treated during weeks 5 to 8 of the CMS protocol with escitalopram. Escitalopram-treated rats with Ͼ20% recovery in the sucrose consumption during the last 2 wk of treatment were defined as escitalopram responders. Rats that did not reach these criteria were defined as escitalopram nonresponders. In the open field test, escitalopram responders demonstrated anxiolytic effect of treatment. In mesenteric small arteries, escitalopram affected neither NO nor cyclooxygenase-1 (COX-1)-mediated vasodilation. Escitalopram potentiated endothelium-dependent hyperpolarization-like response, which was suppressed in the vehicle-treated CMS-susceptible rats and reduced COX-2-dependent relaxation, which was elevated in the vehicle-treated CMS-susceptible rats. Escitalopram did not affect blood pressure and heart rate, which were elevated in the vehicle-treated CMS-susceptible rats. Oxidative stress markers were changed in association with CMS in liver, heart, and brain. Escitalopram normalized oxidative stress markers in the majority of tissues. This study demonstrates that the antidepressant effect of escitalopram is associated with partial improvement of endothelial function in small arteries affecting COX-2 and endothelium-dependent hyperpolarization-like pathways.depression; chronic mild stress; escitalopram; endothelium; nitric oxide synthase; cyclooxygenase; endothelium-derived hyperpolarization; oxidative stress; glutathione; malondialdehyde CARDIOVASCULAR DISEASES AND major depressive disorder are the two most prevalent health problems in high-income countries (31). Their comorbidity is well recognized, but the mechanisms and critical factors underlying this comorbidity are unknown. Interactions between several factors common for both disorders are complex (17; 43). Thus, a dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis and activation of the renin-angiotensin-aldosterone system lead to changes associated with both depression and cardiovascular abnormalities.Also dysfunction of the autonomic nervous system (sympathetic/parasympathetic) is known to be involved, as well as an activation of proinflammatory cytokines (46). Importantly, these factors can induce both depression and ch...

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“…EDH-like relaxation was attenuated in arteries from anhedonic rats. In contrast, in the aorta from CMS mice, approximately one-third of the AChinduced relaxation was via EDH, whereas no EDH response was seen in the aorta from nonstressed mice (29). This difference may reflect species differences or differences between large and small arteries as discussed above.…”

Section: Discussionmentioning

confidence: 80%

“…The observed increase in endothelium-dependent NO signaling in anhedonia could develop consequently to suppression of the EDH-like response, which is the major relaxing pathway in resistant arteries (43). A counterbalancing interaction between EDH and NO signaling has previously been shown in the aorta from CMS mice (29).…”

Section: Discussionmentioning

confidence: 94%

Association Between Endothelial Dysfunction and Depression-Like Symptoms in Chronic Mild Stress Model of Depression

Bouzinova

Nørregaard

Razgovorova

et al. 2014

Psychosomatic Medicine

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Fluoxetine Effect on Aortic Nitric Oxide-Dependent Vasorelaxation in the Unpredictable Chronic Mild Stress Model of Depression in Mice

Abstract: As an independent risk factor, UCMS reproduced the endothelial alterations observed in depression but was not sufficient to provoke morphological alterations.

Cited by 38 publications

References 44 publications

Effects of nitric oxide synthesis inhibitor or fluoxetine treatment on depression-like state and cardiovascular changes induced by chronic variable stress in rats

Effects of nitric oxide synthesis inhibitor or fluoxetine treatment on depression-like state and cardiovascular changes induced by chronic variable stress in rats

Chronic selective serotonin reuptake inhibition modulates endothelial dysfunction and oxidative state in rat chronic mild stress model of depression

Association Between Endothelial Dysfunction and Depression-Like Symptoms in Chronic Mild Stress Model of Depression

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