5-HT in systemic hypertension: foe, friend or fantasy?

Watts, Stephanie W.

doi:10.1042/cs20040364

Cited by 83 publications

(77 citation statements)

References 147 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Fifth, serotonin acts as vasoconstrictor and was reported to inhibit Kv channels in vascular smooth muscle. 20) Although SSRIs may increase the serotonin concentration in the circulation, thereby increasing cardiovascular risk in specific hypertensive patients, 21) this increase in serotonin by SSRIs was not possible in a single cell experimental system. Therefore, the inhibition of Kv current by fluvoxamine was not due to SSRI-induced increases .…”

Section: Discussionmentioning

confidence: 99%

The Effects of the Selective Serotonin Reuptake Inhibitor Fluvoxamine on Voltage-Dependent K<sup>+</sup> Channels in Rabbit Coronary Arterial Smooth Muscle Cells

Hong

Kim

et al. 2015

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

We demonstrated the inhibitory effect of fluvoxamine, a selective serotonin reuptake inhibitor (SSRI), on voltage-dependent K (Kv) channels in freshly isolated rabbit coronary arterial smooth muscle cells using a whole-cell patch clamp technique. Fluvoxamine reduced the amplitude of Kv currents in a concentration-dependent manner with an IC 50 value of 3.71 1.09 µM and a Hill coefficient of 0.62 0.14. Although fluvoxamine did not significantly affect the steady-state activation curve, it shifted the steady-state inactivation curve toward a more negative potential. Pretreatment with another SSRI, paroxetine, did not affect the basal Kv current and did not alter the inhibitory effect of fluvoxamine on Kv channels. We concluded that fluvoxamine inhibits the Kv current in a concentration-dependent manner and in a closed (inactivated) state of the Kv channels independent of serotonin reuptake inhibition.Key words fluvoxamine;voltage-dependentK + channel; coronary artery; smooth muscle; selective serotonin reuptake inhibitorFluvoxamine is a selective serotonin reuptake inhibitor (SSRI) that has been used for the treatment of major depression, anxiety, and panic disorder since 1983 in many countries, including those in Europe and Japan.1,2) The antidepressant activity of fluvoxamine is derived from inhibition of serotonin reuptake in the central nervous system with negligible effects on other neurotransmitter reuptake systems.3,4) A recent study indicated that fluvoxamine showed high affinity for the σ1 receptor, which has a neuromodulatory role on the neurotransmitter system and an antidepressant-like effect. 5-7)Although fluvoxamine has beneficial effects in the treatment of depression, its administration is associated with common side effects, including nausea, anorexia, palpitations, headache, and dizziness. 8)Fluvoxamine also affects ion channels, such as the human ether-a-go-go related (hERG) K + and Kv1.5 channels. 9,10) However, these studies were performed primarily in cultured cell lines rather than in native cells. Therefore, questionsremainabouttheeffectoffluvoxamineonionchannels from freshly isolated cells, particularly vascular smooth muscle cells. 11,12) Our previous reports suggested that Kv channels participate in the regulation of resting membrane potential and thus resting tone in some arteries. 13,14) In addition, pathological states such as hypertension, diabetes, and hypoxia, are closely related with alteration of Kv channel activity and expression in the vasculature.15) Therefore, the adverse effects of drugs on Kv channels should be clearly determined to correctly interpret experimental data regarding vascular disorders.Considering the usefulness of fluvoxamine as a SSRI and the physiological importance of Kv channels, the effects of fluvoxamine on vascular Kv channel should be clearly examined to avoid toxic effect on the vasculature when applying fluvoxamineasantidepressantdrug.In the present study, we investigated the effects of fluvoxamine on Kv channels using freshly isolated coronary ...

show abstract

Section: Discussionmentioning

confidence: 99%

The Effects of the Selective Serotonin Reuptake Inhibitor Fluvoxamine on Voltage-Dependent K<sup>+</sup> Channels in Rabbit Coronary Arterial Smooth Muscle Cells

Hong

Kim

et al. 2015

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

show abstract

“…Serotonin is a potent vasoconstrictor, and up-regulation of serotonin production may have deleterious effects on placental blood supply and there has been a major concern that use of fluoxetine, a selective serotonin reuptake inhibitor during pregnancy affects foetal growth and development. [50,51]. PEPCK is a key regulator of gluconeogenesis and hyperglycemia is a well-known side effect of steroid use.…”

Section: Discussionmentioning

confidence: 99%

Antenatal Dexamethasone Treatment Leads to Changes in Gene Expression in a Murine Late Placenta

Baisden

Sonne

Joshi³

et al. 2007

Placenta

View full text Add to dashboard Cite

Antenatal steroids like dexamethasone (DEX) are used to augment foetal lung maturity and there is a major concern that they impair foetal growth. If delivery is delayed after using antenatal DEX, placental function and hence foetal growth may be compromised even further. To investigate the effects of DEX on placental function, we treated 9 pregnant C57/BL6 mice with DEX and 9 pregnant mice were injected with saline to serve as controls. Placental gene expression was studied using microarrays in 3 pairs and other 6 pairs were used to confirm microarray results by semi-quantitative RT-PCR, real-time PCR, in situ hybridization, western blot analysis and Oligo ApopTaq assay. DEXtreated placentas were hydropic, friable, pale, and weighed less (80.0±15.1 mg compared to 85.6.8 ±7.6 mg, p=0.05) (n=62 placentas). Foetal weight was significantly reduced after DEX use (940±32 mg compared to 1162±79 mg, p=0.001) (n=62 foetuses). There was > 99% similarity within and between the three gene chip data sets. DEX led to down-regulation of 1212 genes and up-regulation of 1382 genes. RT-PCR studies showed that DEX caused a decrease in expression of genes involved in cell division such as cyclins A2, B1, D2, cdk 2, cdk 4 and M-phase protein kinase along with growth-promoting genes such as EGF-R, BMP4 and IGFBP3. Oligo ApopTaq assay and western blot studies showed that DEX-treatment increased apoptosis of trophoblast cells. DEX-treatment led to up-regulation of aquaporin 5 and tryptophan hydroxylase genes as confirmed by real-time PCR, and in situ hybridization studies. Thus antenatal DEX treatment led to a reduction in placental and foetal weight, and this effect was associated with a decreased expression of several growth-promoting genes and increased apoptosis of trophoblast cells.

show abstract

“…Reasons for choosing this model include an identified dependence of this model on serotonergic receptor stimulation (Watts and Fink, 1999) and established supersensitivity of arteries to 5-HT (Watts, 2005). Mineralocorticoid dependence grows increasingly recognized as a potential cause of essential hypertension, and thus this is a valuable model to study (Funder 2007).…”

Section: Introductionmentioning

confidence: 99%

“…Tissues also take up and concentrate 5-HT via SERT (Ni et al, 2004;. 5-HT acts as both a dilator and constrictor of the arterial circulation (Watts, 2005).…”

Section: Introductionmentioning

confidence: 99%

“…These include that 1) plasma levels (free) of 5-HT are higher in multiple forms of human hypertension including preeclampsia and essential hypertension (Brenner et al, 2007;Carrasco et al, 1998;Fetkovska et al, 1990); 2) SERT inhibitors such as fluoxetine cause an increase in blood pressure (Amsterdam et al, 1999;Lazartigues et al, 2000); 3) the ability of arteries to take up 5-HT through SERT is impaired in hypertension (Fetkovska et al, 1990;; and 4) arteries from hypertensive humans and experimental models are hyperresponsive to 5-HT (for review, see Watts 2005). The necessity of SERT in pulmonary hypertension is well established (MacLean, 2007).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Lack of the serotonin transporter does not prevent mineralocorticoid hypertension in rat and mouse

Zhou

Diaz

et al. 2008

European Journal of Pharmacology

View full text Add to dashboard Cite

We hypothesized that lack of a functional serotonin transporter (SERT) would increase basal blood pressure and enhance the development of deoxycorticosterone acetate (DOCA)-salt hypertension compared to wild type (WT) controls. Mean arterial blood pressure was measured in WT and SERT knockout (KO) mice and rat models through radiotelemetry. Basal blood pressures were not different between respective WT and KO. Moreoever, blood pressure elevated similarly (~50 mm Hg) in all strains given DOCA and salt. Thus, the lack of functional SERT did not prevent development of DOCA-salt induced hypertension or modify basal blood pressure significantly.

show abstract

5-HT in systemic hypertension: foe, friend or fantasy?

Cited by 83 publications

References 147 publications

The Effects of the Selective Serotonin Reuptake Inhibitor Fluvoxamine on Voltage-Dependent K<sup>+</sup> Channels in Rabbit Coronary Arterial Smooth Muscle Cells

The Effects of the Selective Serotonin Reuptake Inhibitor Fluvoxamine on Voltage-Dependent K<sup>+</sup> Channels in Rabbit Coronary Arterial Smooth Muscle Cells

Antenatal Dexamethasone Treatment Leads to Changes in Gene Expression in a Murine Late Placenta

Lack of the serotonin transporter does not prevent mineralocorticoid hypertension in rat and mouse

Contact Info

Product

Resources

About