Contribution of oxidative stress and prostanoids in endothelial dysfunction induced by chronic fluoxetine treatment

doi:10.1016/j.vph.2015.06.015

Vascular Pharmacology

Volume 73, October 2015, Pages 124-137

https://doi.org/10.1016/j.vph.2015.06.015 Get rights and content

Abstract

Objectives

The effects of chronic fluoxetine treatment were investigated on blood pressure and on vascular reactivity in the isolated rat aorta.

Methods and results

Male Wistar rats were treated with fluoxetine (10 mg/kg/day) for 21 days. Fluoxetine increased systolic blood pressure. Chronic, but not acute, fluoxetine treatment increased the contractile response induced by phenylephrine, serotonin (5-HT) and KCl in endothelium-intact rat aortas. l-NAME and ODQ did not alter the contraction induced by phenylephrine and 5-HT in aortic rings from fluoxetine-treated rats. Tiron, SC-560 and AH6809 reversed the increase in the contractile response to phenylephrine and 5-HT in aortas from fluoxetine-treated rats. Fluoxetine treatment increased superoxide anion generation (O₂⁻) and the expression of cyclooxygenase (COX)-1 in the rat aorta. Reduced expression of nNOS, but not eNOS or iNOS was observed in animals treated with fluoxetine. Fluoxetine treatment increased prostaglandin (PG)F_2α levels but did not affect thromboxane (TX)B₂ levels in the rat aorta. Reduced hydrogen peroxide (H₂O₂) levels and increased catalase (CAT) activity were observed after treatment.

Conclusions

The major new finding of our study is that chronic fluoxetine treatment induces endothelial dysfunction, which alters vascular responsiveness by a mechanism that involves increased oxidative stress and the generation of a COX-derived vasoconstrictor prostanoid (PGF_2α). Moreover, our results evidenced a relation between the period of treatment with fluoxetine and the magnitude in the increment of blood pressure. Finally, our findings raise the possibility that fluoxetine treatment increases the risk for vascular injury, a response that could predisposes to cardiovascular diseases.

Graphical abstract

Introduction

Cardiovascular mortality in patients taking psychotropic drugs is high. Tricyclic antidepressants (TCAs), among others, are associated with increased risk of cardiac arrhythmias and death [1]. Fluoxetine belongs to a class of new generation antidepressants which are collectively know as selective serotonin (5-HT) reuptake inhibitors (SSRIs). Those drugs are considered to be free from the cardiotoxic effects of TCAs. However, mounting evidences suggest that SSRIs induce cardiovascular dysfunction such as arrhythmias, electrocardiogram abnormalities and rest bradycardia [2], [3], [4]. Fluoxetine displayed potent inhibitory properties on Na⁺, Ca^2 + and K⁺ channels in cardiac tissue in vitro [5]. More recently, treatment with fluoxetine for 21 days was showed to induce mild hypertension and enhanced baroreflex responses associated with bradycardia [6]. The cardiac effects of fluoxetine are well characterized, but information regarding the effects of SSRIs on the vasculature is limited.

Ungvari et al. [7] showed that fluoxetine induced endothelium-independent relaxation of isolated rat cerebral arteries. Moreover, fluoxetine inhibited the contraction induced by 5-HT, noradrenaline and Bay K 8644, a voltage-dependent Ca^2 + channel opener, further suggesting that fluoxetine blocks Ca^2 + channels in the vascular smooth muscle. Similar results were observed in arterioles from rat skeletal muscle where fluoxetine reduced intracellular Ca^2 + concentration [8]. Although in vitro studies have shown that fluoxetine affects vascular reactivity to vasoconstrictor agents, there is no evidence on the effect of chronic fluoxetine treatment on vascular responsiveness to vasoactive agents.

The vascular endothelium is important in the maintenance of the vascular tone since it is responsible for the production of endothelial-derived mediators involved in the contraction and relaxation of the vasculature [9]. Endothelial dysfunction results in impaired endothelium-mediated vasodilatation, increased vascular reactivity and is associated with several pathologies in the cardiovascular system, including hypertension [10]. Decreased nitric oxide (NO) bioavailability together with increased reactive oxygen species (ROS) generation contributes to the molecular events underlying endothelial dysfunction [9]. Interestingly, fluoxetine was described to reduce NO release by synovial and striatal cells [11], [12]. Moreover, fluoxetine was also shown to reduce the expression of the enzyme NO synthase (NOS) in the rat hippocampus [13]. More recently, Göçmez et al. [14] suggested that chronic fluoxetine treatment impairs the synthesis or availability of NO in the corpus cavernosum. Another interesting observation is that fluoxetine induced ROS generation in human hepatocytes [15]. However, whether fluoxetine treatment increases ROS generation and reduces NO bioavailability in the vasculature remains elusive.

Since fluoxetine reduces NO bioavailability and increases ROS generation in different tissues, we hypothesized that fluoxetine treatment would induce endothelial dysfunction. Although the acute effect of fluoxetine in the vasculature in vitro was previously described, to the best of our knowledge, no studies have evaluated the effect of chronic fluoxetine treatment in the vasculature. In the present study, we investigated the effect of fluoxetine in the responsiveness of the isolated rat aorta and the mechanisms underlying such effect.

Section snippets

Experimental design

Male Wistar rats were housed under standard laboratory conditions with free access to food and water. The housing conditions and experimental protocols were approved by the Animal Ethics Committee of the University of São Paulo — Campus of Ribeirão Preto (#11.1.1593.53.9) and were performed in accordance with the Brazilian animal protection laws and institutional guidelines. The rats, initially weighing 230–260 g (50–60 days old), were randomly divided into two groups: Chronic vehicle: daily

Body weight

Before treatment, rats showed mean body masses of 257 ± 4 g (control group) and 245 ± 4 g (fluoxetine). After treatment for 21 days, no variation in body mass was observed in animals between the two experimental groups: 407 ± 7 g (control n = 40) and 395 ± 6 g (fluoxetine n = 40).

Effect of chronic treatment with fluoxetine on blood pressure

Baseline values of systolic blood pressure were similar in control (119 ± 1 mm Hg, n = 10) and fluoxetine-treated animals (120 ± 1 mm Hg, n = 10). Significant increased blood pressure was observed in 7-days fluoxetine-treated animals. This

Discussion

Our findings showing that chronic treatment with fluoxetine increased systolic blood pressure are in accordance with previous experimental and clinical studies [4], [6], [24]. Importantly, we first demonstrated a time-course for blood pressure increase associated with fluoxetine treatment. Significant blood pressure increase concomitant with fluoxetine was already observed after 7 days of treatment and up until day 15 at which time a sustained plateau is reached. Thus, results presented here

Conflict of interest

None declared.

Acknowledgments

We acknowledge L.H.A. de Camargo for technical support. This work was supported by funds from Fundação de Amparo à Pesquisa do Estado de São Paulo — FAPESP (#2010/05815-4 and #2013/00808-8) and NAP-DIN (#11.1.21625.01.0). J.A.S. is supported by a master fellowship from CAPES.

References (48)

C.C. Crestani et al.
Chronic fluoxetine treatment alters cardiovascular functions in unanesthetized rats
Eur. J. Pharmacol.
(2011)
F. Crespi
The selective serotonin reuptake inhibitor fluoxetine reduces striatal in vivo levels of voltammetric nitric oxide (NO): a feature of its antidepressant activity?
Neurosci. Lett.
(2010)
S.S. Göçmez et al.
Chronic administration of fluoxetine impairs neurogenic and endothelium-dependent relaxation of the rabbit corpus cavernosum smooth muscle
Eur. J. Pharmacol.
(2011)
N. Laville et al.
Effects of human pharmaceuticals on cytotoxicity, EROD activity and ROS production in fish hepatocytes
Toxicology
(2004)
C. Lino-de-Oliveira et al.
Effects of acute and chronic fluoxetine treatments on restraint stress-induced Fos expression
Brain Res. Bull.
(2001)
A. Yogi et al.
Acute ethanol intake induces superoxide anion generation and mitogen-activated protein kinase phosphorylation in rat aorta: a role for angiotensin type 1 receptor
Toxicol. Appl. Pharmacol.
(2012)
N.A. Gonzaga et al.
Ethanol withdrawal increases oxidative stress and reduces nitric oxide bioavailability in the vasculature of rats
Alcohol
(2015)
H. Aebi
Catalase in vitro
Methods Enzymol.
(1984)
B.R. Silva et al.
Phenylephrine activates eNOS Ser(1177) phosphorylation and nitric oxide signaling in renal hypertensive rat aorta
Eur. J. Pharmacol.
(2014)
M. Kesavan et al.
Atorvastatin restores arsenic-induced vascular dysfunction in rats: modulation of nitric oxide signaling and inflammatory mediators
Toxicol. Appl. Pharmacol.
(2014)

M. Denniff et al.

The time-of-day variation in vascular smooth muscle contractility depends on a nitric oxide signalling pathway

J. Mol. Cell. Cardiol.

(2014)

S. Novella et al.

Aging-related endothelial dysfunction in the aorta from female senescence-accelerated mice is associated with decreased nitric oxide synthase expression

Exp. Gerontol.

(2013)

A. Chatterjee et al.

Endothelial nitric oxide (NO) and its pathophysiologic regulation

Vasc. Pharmacol.

(2008)

L. Pernomian et al.

The role of reactive oxygen species in the modulation of the contraction induced by angiotensin II in carotid artery from diabetic rat

Eur. J. Pharmacol.

(2012)

B.R. Silva et al.

Hydrogen peroxide modulates phenylephrine-induced contractile response in renal hypertensive rat aorta

Eur. J. Pharmacol.

(2013)

I. Fridovich

Superoxide anion radical (O₂⁻.), superoxide dismutases, and related matters

J. Biol. Chem.

(1997)

M. Bauer et al.

World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for Biological Treatment of Unipolar Depressive Disorders, part 1: acute and continuation treatment of major depressive disorder

World J. Biol. Psychiatry

(2002)

S.A. Spier et al.

Unexpected deaths in depressed medical in patients treated with fluoxetine

J. Clin. Psychiatry

(1991)

T. Ravina et al.

Fluoxetine-induced QTU interval prolongation, T wave alternans and syncope

Int. J. Cardiol.

(1998)

S.P. Roose et al.

Cardiovascular effects of fluoxetine in depressed patients with heart disease

Am. J. Psychiatry

(1998)

P. Pacher et al.

Cardiovascular side effects of new antidepressants and antipsychotics: new drugs, old concerns?

Curr. Pharm. Des.

(2004)

Z. Ungvari et al.

Fluoxetine dilates isolated small cerebral arteries of rats and attenuates constrictions to serotonin, norepinephrine, and a voltage-dependent Ca(2 +) channel opener

Stroke

(1999)

Z. Ungvari et al.

Serotonin reuptake inhibitor fluoxetine decreases arteriolar myogenic tone by reducing smooth muscle [Ca^2 +]_i

J. Cardiovasc. Pharmacol.

(2000)

A.C. Montezano et al.

Reactive oxygen species and endothelial function — role of nitric oxide synthase uncoupling and Nox family nicotinamide adenine dinucleotide phosphate oxidases

Basic Clin. Pharmacol. Toxicol.

(2012)

Cited by (24)

Changes in blood pressure after introduction of an antidepressant in a public institution of mental health
2020, Annales de Cardiologie et d'Angeiologie
La primo-prescription d’antidépresseur est fréquente en médecine générale. La relation entre introduction d’antidépresseur et évolution de la pression artérielle (PA) n’est pas bien établie dans la littérature. Nous avons étudié l’évolution à court terme de la PA en fonction de l’introduction, ou non, d’un antidépresseur au sein d’un établissement public de santé mentale (EPSM).
Étude épidémiologique analytique monocentrique de type exposé/non exposé sur une cohorte rétrospective, avec un recueil des données des séjours entre 2013 et 2015 à l’EPSM d’Armentières. Les séjours ont été séparés en deux groupes : traité par antidépresseur (introduit lors du séjour) et témoin (sans antidépresseur). La PA a été mesurée sur une période de 30 jours par séjour. Pour évaluer l’évolution de la PA en fonction des groupes, nous avons utilisé un modèle de régression linéaire, mixte imbriqué, avec ajustement sur plusieurs variables.
Sur 1241 séjours analysés, 124 étaient dans le groupe traité et 1117 dans le groupe témoin. L’âge moyen des patients était de 44,6 ± 14,7 ans. Les deux groupes étaient comparables sur la plupart des variables analysées. La variation de PA systolique était associée aux valeurs de PA systolique à l’entrée, à l’antécédent d’HTA, à la présence d’un antihypertenseur et à l’IMC ; la variation de PA diastolique était associée aux valeurs de PA diastolique à l’entrée, à la présence d’un antihypertenseur, à l’IMC et à l’antécédent de trouble bipolaire. Nous ne retrouvons pas de différence significative dans l’évolution de la PA dans le temps entre le groupe traité et le groupe témoin sur les 30 jours de mesure par séjour, après ajustement (coefficient d’évolution de +0,12 mmHg de PA systolique et −0,1 mmHg de PA diastolique, p = 0,45 et 0,38 respectivement).
Ces résultats sont rassurants sur l’évolution précoce de la PA après introduction d’antidépresseur. Ils ne doivent pas faire oublier les effets fréquents de la dépression et des antidépresseurs sur le risque cardiovasculaire (diminution de l’activité physique, dyslipidémie, prise de poids, etc.)
Primary prescribing of antidepressants is common in general practice. The relationship between antidepressant introduction and blood pressure (BP) changes is not well established in the literature. The purpose of our study was to examine the short-term course of AHR with and without the introduction of an antidepressant into a public institution of mental health (EPSM).
An exposed/non-exposed single-centre analytical epidemiological study on a retrospective cohort, with a collection of data on stays between 2013 and 2015 at the EPSM in Armentières. The stays were divided into two groups: antidepressant treatment (introduced during the stay) and control (without antidepressant). BP measurements were taken over a 30-day period per stay. To assess the evolution of AHR across groups, we used a nested mixed linear regression model with multivariate adjustment.
Out of 1241 stays analysed, 124 were in the treated group and 1117 in the control group. The average age was 44.6 ± 14.7 years. The two groups were comparable on most of the variables analyzed. The change in systolic BP was associated with systolic BP values at baseline, history of hypertension, presence of an antihypertensive drug and BMI; the change in diastolic BP was associated with diastolic BP values at baseline, presence of an antihypertensive drug, BMI and history of bipolar disorder. We find no significant difference in the evolution of BP over time between the treated group and the control group over the 30 days of measurement per stay, after adjustment (evolution coefficient of +0.12 mmHg systolic BP and −0.1 mmHg diastolic BP, P = 0.45 and 0.38 respectively).
These results are reassuring on the early development of BP after the introduction of antidepressants. They should not overlook the frequent effects of depression and antidepressants on cardiovascular risk (decreased physical activity, dyslipidemia, weight gain, etc.).
Treatment with nitrite prevents reactive oxygen species generation in the corpora cavernosa and restores intracavernosal pressure in hypertensive rats
2020, Nitric Oxide - Biology and Chemistry
Hypertension is a risk factor for erectile dysfunction (ED) and both conditions are associated with oxidative stress. Given that nitrite is described to display antioxidant effects, we hypothesized that treatment with nitrite would exert antioxidant effects attenuating both reactive oxygen species (ROS) generation in the corpora cavernosa (CC) and ED induced by hypertension. Two kidney, one clip (2K1C) hypertension was induced in male Wistar rats. Treatment with sodium nitrite (15 mg/kg/day, p.o., gavage) was initiated two weeks after surgery to induce hypertension and maintained for four weeks. Nitrite abrogated both the decrease in intracavernosal pressure and endothelial dysfunction of the CC induced by hypertension. Treatment with nitrite decreased hypertension-induced ROS generation in the CC assessed in situ using the fluorescent dye dihidroethidium (DHE) and with the lucigenin assay. Western immunoblotting analysis revealed that nitrite prevented the increase in Nox1 expression in the CC from 2K1C rats. Decreased concentrations of hydrogen peroxide (H₂O₂) were found in the CC from hypertensive rats and treatment with nitrite prevented this response. Treatment with nitrite increased the fluorescence of DAF-2DA in the CC from sham-operated rats and restored nitric oxide (NO) levels in the CC from 2K1C rats. In summary, we found novel evidence that nitrite reversed the decrease in intracavernosal pressure induced by 2K1C hypertension. This response was partially attributed to the antioxidant effect of nitrite that blunted ROS generation and endothelial dysfunction in the CC. In addition, nitrite-derived NO may have promoted direct protective actions against hypertension-induced CC dysfunction.
Icariin protects vascular endothelial cells from oxidative stress through inhibiting endoplasmic reticulum stress
2019, Journal of Integrative Medicine
To investigate the protective effect and underlying mechanism(s) of icariin (ICA) in preventing hydrogen peroxide (H₂O₂)-induced vascular endothelial cell injury via endoplasmic reticulum stress (ERS).
To study the effects of ICA on H₂O₂-induced damage, we used the cell counting kit-8 assay to detect cell viability and the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay to determine cell adhesion and apoptosis, respectively. Spectrophotometry and enzyme-linked immunosorbent assay were used to measure the expression levels of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). Subsequently, glucose-regulated protein 78 (GRP78), activating transcription factor-4 (ATF4) and eukaryotic initiation factor-2α (eIF2α) were detected using Western blotting.
In human umbilical vein endothelial cells, different concentrations of ICA exhibited multiple effects, including reduced H₂O₂ damage, improved cell viability and adhesion, reduced cell apoptosis and increased SOD and GSH-Px activity. Among the ICA concentrations used, only the H₂O₂ + 100 μmol/L ICA group had significant differences compared to the H₂O₂ group. ERS activators H₂O₂ and dl-dithiothreitol (DTT) significantly increased GRP78, ATF4 and eIF2α expressions, decreased cell activity and reduced SOD and GSH-Px activity. In contrast, the H₂O₂ + 100 μmol/L ICA and H₂O₂ + 100 μmol/L ICA + DTT groups had significant inhibitory effects on the expressions of GRP78, ATF4 and eIF2α proteins, showing enhanced cell viability and SOD and GSH-Px activity.
The results showed the dose-dependent effects of ICA against H₂O₂-induced injury in vascular endothelial cells. The inhibition of GRP78, ATF4 and eIF2α protein expressions in the ERS, and the subsequent alleviation of oxidative stress damage, might be the molecular mechanism.
Chronic ethanol consumption increases vascular oxidative stress and the mortality induced by sub-lethal sepsis: Potential role of iNOS
2018, European Journal of Pharmacology
Citation Excerpt :
The results are shown as nmol/mg protein or nmol/ml of plasma. Plasma and MAB supernatants were used for the determination of SOD or CAT activities and GSH levels as previously described (Gonzaga et al., 2014; Simplicio et al., 2015). Briefly, SOD activity was determined following instructions of a commercially available kit (#19160, Sigma-Aldrich, St. Louis, MO, USA), and results are shown as % inhibition rate/mg protein or % inhibition rate/ml of plasma.
We hypothesized that long-term ethanol consumption would increase the mortality and aggravate the deleterious effects of sub-lethal cecal ligation and puncture (SL-CLP) in the vasculature by inducing the expression of inducible nitric oxide (NO) synthase (iNOS). Male C57BL/6J wild-type (WT) or iNOS-deficient mice (iNOS^-/-) were treated with ethanol (20% v/v) for 12 weeks and then subjected to SL-CLP. Mice were killed 24 h post-operatively or followed six days for survival. Septic ethanol-treated mice showed a higher mortality than septic WT mice. However, septic iNOS-deficient mice treated with ethanol showed a decreased mortality rate when compared to ethanol-treated WT mice. Ethanol and SL-CLP augmented superoxide anion (O₂^-) generation in the mesenteric arterial bed (MAB) of both WT and iNOS-deficient mice. Treatment with ethanol and SL-CLP enhanced lipoperoxidation in the MAB of WT, but not iNOS-deficient mice. SL-CLP enhanced nitrate/nitrite (NOx) concentrations in the MAB of WT, but not iNOS-deficient mice. Both, ethanol and SL-CLP increased TNF-α and IL-6 levels in the MAB. Treatment with ethanol as well as SL-CLP up-regulated the expression of iNOS in the MAB of WT mice. The major finding of our study is that chronic ethanol consumption increases the mortality induced by SL-CLP and that iNOS plays a role in such response. Although ethanol led to vascular alterations, it did not aggravate the vascular injury induced by SL-CLP. Finally, iNOS mediated the increase in oxidative stress and pro-inflammatory cytokines induced by SL-CLP in the vasculature.
Olive oil and leaf extract prevent fluoxetine-induced hepatotoxicity by attenuating oxidative stress, inflammation and apoptosis
2018, Biomedicine and Pharmacotherapy
Citation Excerpt :
Other studies have showed fluoxetine-induced cholestasis, steatosis, portal zone inﬂammation, lobular inﬂammation and hepatomegaly [6–9]. Fluoxetine administration was associated with oxidative stress as reported in different studies [10–12]. Olive oil and olive leaf extract are gaining interest on nutritional therapy.
Olive oil and leaf extract have several health benefits; however, their beneficial effect against fluoxetine-induced liver injury has not been investigated. The present study aimed to scrutinize the impact of fluoxetine on the liver of rats and to evaluate the protective effects of olive oil and leaf extract. Rats received fluoxetine orally at dose of 10 mg/kg body weight for 7 consecutive days. The fluoxetine-induced rats were concurrently treated with olive oil or leaf extract. At the end of the experiment, blood and liver samples were collected for analysis. Fluoxetine administration significantly increased circulating ALT, AST, ALP and the pro-inflammatory cytokines TNF-α and IL-1β levels in rats. Histological analysis showed several alterations, such as inflammatory cells infiltration, hepatocyte vacuolation and dilated sinusoids in the liver of fluoxetine-induced rats. Concurrent supplementation of olive oil and olive leaf extract significantly reduced circulating liver function marker enzymes and pro-inflammatory cytokines, and prevented fluoxetine-induced histological alterations. Both olive oil and leaf extract significantly decreased liver lipid peroxidation and nitric oxide, and ameliorated liver glutathione, superoxide dismutase, catalase and glutathione peroxidase. In addition, olive oil and leaf extract prevented fluoxetine-induced apoptosis in the liver of rats as evidenced by decreased expression of Bax and caspase-3, and up-regulated expression of Bcl-2. In conclusion, olive oil and leaf extract protect against ﬂuoxetine-induced liver injury in rats through attenuation of oxidative stress, inflammation and apoptosis.
Mechanisms underlying sodium nitroprusside-induced tolerance in the mouse aortaRole of ROS and cyclooxygenase-derived prostanoids
2017, Life Sciences
Citation Excerpt :
Activity of SOD was evaluated in control and endothelium-denuded tolerant arteries (after incubation or not with tiron). The SOD activity was evaluated using a commercially available kit (#19160, Sigma-Aldrich, St. Louis, MO, USA) as previously described [34]. The results were normalized for protein concentration and SOD activity is expressed as % inhibition rate/mg protein.
To determine the role of reactive oxygen species (ROS) on sodium nitroprusside (SNP)-induced tolerance. Additionally, we evaluated the role of ROS on NF-κB activation and pro-inflammatory cytokines production during SNP-induced tolerance.
To induce in vitro tolerance, endothelium-intact or -denuded aortic rings isolated from male Balb-c mice were incubated for 15, 30, 45 or 60 min with SNP (10 nmol/L).
Tolerance to SNP was observed after incubation of endothelium-denuded, but not endothelium-intact aortas for 60 min with this inorganic nitrate. Pre-incubation of denuded rings with tiron (superoxide anion (O₂⁻) scavenger), and the NADPH oxidase inhibitors apocynin and atorvastatin reversed SNP-induced tolerance. l-NAME (non-selective NOS inhibitor) and l-arginine (NOS substrate) also prevented SNP-induced tolerance. Similarly, ibuprofen (non-selective cyclooxygenase (COX) inhibitor), nimesulide (selective COX-2 inhibitor), AH6809 (prostaglandin PGF₂α receptor antagonist) or SQ29584 [PGH₂/thromboxane TXA₂ receptor antagonist] reversed SNP-induced tolerance. Increased ROS generation was detected in tolerant arteries and both tiron and atorvastatin reversed this response. Tiron prevented tolerance-induced increase on O₂^– and hydrogen peroxide (H₂O₂) levels. The increase onp65/NF-κB expression and TNF-α production in tolerant arteries was prevented by tiron. The major new finding of our study is that SNP-induced tolerance is mediated by NADPH-oxidase derived ROS and vasoconstrictor prostanoids derived from COX-2, which are capable of reducing the vasorelaxation induced by SNP. Additionally, we found that ROS mediate the activation of NF-κB and the production of TNF-α in tolerant arteries.
These findings identify putative molecular mechanisms whereby SNP induces tolerance in the vasculature.

View all citing articles on Scopus

View full text

Contribution of oxidative stress and prostanoids in endothelial dysfunction induced by chronic fluoxetine treatment

Abstract

Objectives

Methods and results

Conclusions

Graphical abstract

Introduction

Section snippets

Experimental design

Body weight

Effect of chronic treatment with fluoxetine on blood pressure

Discussion

Conflict of interest

Acknowledgments

Eur. J. Pharmacol.

Neurosci. Lett.

Eur. J. Pharmacol.

Toxicology

Brain Res. Bull.

Toxicol. Appl. Pharmacol.

Alcohol

Methods Enzymol.

Eur. J. Pharmacol.

Toxicol. Appl. Pharmacol.

J. Mol. Cell. Cardiol.

Exp. Gerontol.

Vasc. Pharmacol.

Eur. J. Pharmacol.

Eur. J. Pharmacol.

J. Biol. Chem.

World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for Biological Treatment of Unipolar Depressive Disorders, part 1: acute and continuation treatment of major depressive disorder

World J. Biol. Psychiatry

Unexpected deaths in depressed medical in patients treated with fluoxetine

J. Clin. Psychiatry

Fluoxetine-induced QTU interval prolongation, T wave alternans and syncope

Int. J. Cardiol.

Cardiovascular effects of fluoxetine in depressed patients with heart disease

Am. J. Psychiatry

Cardiovascular side effects of new antidepressants and antipsychotics: new drugs, old concerns?

Curr. Pharm. Des.

Fluoxetine dilates isolated small cerebral arteries of rats and attenuates constrictions to serotonin, norepinephrine, and a voltage-dependent Ca(2 +) channel opener

Stroke

Serotonin reuptake inhibitor fluoxetine decreases arteriolar myogenic tone by reducing smooth muscle [Ca2 +]i

J. Cardiovasc. Pharmacol.

Reactive oxygen species and endothelial function — role of nitric oxide synthase uncoupling and Nox family nicotinamide adenine dinucleotide phosphate oxidases

Basic Clin. Pharmacol. Toxicol.

Serotonin reuptake inhibitor fluoxetine decreases arteriolar myogenic tone by reducing smooth muscle [Ca^2 +]_i