Differential regulation of K+ and Ca2+ channel gene expression by chronic treatment with estrogen and tamoxifen in rat aorta

Tsang, Suk Ying; Yao, Xiaoqiang; Wong, Chi Ming; Chan, Franky L.; Chen, Zhenyu; Huang, Yü

doi:10.1016/j.ejphar.2003.10.031

Cited by 27 publications

(14 citation statements)

References 40 publications

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“…Enhanced vasoconstriction to membrane depolarization in ovariectomized arteries raises the possibility that oestrogen deficiency may upregulate the function or expression of L‐type Ca 2+ channels in VSMC. This is supported, in part, by the fact that relaxing sensitivity to nicardipine is greater after ovariectomy and the enhanced dilatation is normalized by treatment with oestrogen 47 . Ovariectomy increases the mRNA expression of the α 1C ‐subunit of L‐type Ca 2+ channels in VSMC, which is prevented by chronic treatment with tamoxifen or oestrogen 47 .…”

Section: Tamoxifen and Vascular Tonementioning

confidence: 95%

“…This is supported, in part, by the fact that relaxing sensitivity to nicardipine is greater after ovariectomy and the enhanced dilatation is normalized by treatment with oestrogen 47 . Ovariectomy increases the mRNA expression of the α 1C ‐subunit of L‐type Ca 2+ channels in VSMC, which is prevented by chronic treatment with tamoxifen or oestrogen 47 . In addition, the effect of combined treatment with oestrogen and tamoxifen is not summative.…”

Section: Tamoxifen and Vascular Tonementioning

confidence: 97%

“…Tamoxifen activates large‐conductance Ca 2+ ‐activated K + (K Ca ) channels through interaction with the regulatory β 1 ‐subunit in smooth muscle cells 46 . However, chronic treatment with tamoxifen does not affect the mRNA expression of either the α‐ or β‐subunits of BK Ca channels in rat aortas 47 . Given the functional importance of the K Ca channel β 1 ‐subunit in the regulation of vascular tone, it is crucial to elucidate the exact role of K Ca channels in tamoxifen‐induced VSMC relaxation or hyperpolarization in intact arteries 48 .…”

Section: Tamoxifen and Vascular Tonementioning

confidence: 99%

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Raloxifene, Tamoxifen and Vascular Tone

Leung¹,

Tsang

Wong³

et al. 2007

Clin Exp Pharma Physio

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1. Oestrogen deficiency causes progressive reduction in endothelial function. Despite the benefits of hormone-replacement therapy (HRT) evident in earlier epidemiological studies, recent randomized trials of HRT for the prevention of heart disease found no overall benefit. Instead, HRT users had higher incidences of stroke and heart attack. Most women discontinue HRT because of its many side-effects and/or the increased risk of breast and uterine cancer. This has contributed to the development of selective oestrogen receptor modulators (SERMs), such as tamoxifen and raloxifene, as alternative oestrogenic agents. 2. A SERM is a molecule that binds with high affinity to oestrogen receptors but has tissue-specific effects distinct from oestrogen, acting as an oestrogen agonist in some tissues and as an antagonist in others. Clinical and animal studies suggest multiple cardiovascular effects of SERMs. For example, raloxifene lowers serum levels of cholesterol and homocysteine, attenuates oxidation of low-density lipoprotein, inhibits endothelial-leucocyte interaction, improves endothelial function and reduces vascular smooth muscle tone. 3. Available evidence suggests that raloxifene and tamoxifen are capable of acting directly on both endothelial cells and the underlying vascular smooth muscle cells and cause a multitude of favourable modifications of the vascular wall, which jointly contribute to improved local blood flow. The outcome of the Raloxifene Use for the Heart (RUTH) trial will determine whether raloxifene, currently approved for the treatment of post-menopausal osteoporosis, could substitute for HRT in alleviating cardiovascular symptoms in post-menopausal women.

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Section: Tamoxifen and Vascular Tonementioning

confidence: 95%

Section: Tamoxifen and Vascular Tonementioning

confidence: 97%

Section: Tamoxifen and Vascular Tonementioning

confidence: 99%

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Raloxifene, Tamoxifen and Vascular Tone

Leung¹,

Tsang

Wong³

et al. 2007

Clin Exp Pharma Physio

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“…Laboratory studies in animals also support the theory that tamoxifen induces oestrogen‐like effects in the vascular system. Chronic tamoxifen treatment inhibits constrictor responses to endothelin‐1 (Tsang et al ., 2004a) and to phenylephrine (Thorin et al ., 2003) in cerebral arteries of ovariectomized rats. Tamoxifen acutely inhibits voltage‐gated Ca 2+ currents in aortic smooth muscle cells (Song et al ., 1996).…”

Section: Introductionmentioning

confidence: 99%

Tamoxifen dilates porcine coronary arteries: roles for nitric oxide and ouabain‐sensitive mechanisms

Leung

Yung

Leung

et al. 2006

British J Pharmacology

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Background and purpose: Experiments were designed to determine the mechanism of the relaxation induced by tamoxifen in porcine coronary arteries at the tissue, cellular and molecular levels. . L-Arginine reversed the effect of L-NAME while indomethacin was without effect. Tamoxifen-induced relaxation was attenuated by charybdotoxin (CTX) plus apamin, ouabain or by incubation in a K þ -free solution. Moreover, tamoxifen triggered extracellular Ca 2 þ -dependent increases in endothelial [Ca 2 þ ] i and this effect was abolished by ICI 182,780. Endothelium-independent relaxation to sodium nitroprusside was also inhibited by ouabain or in a K þ -free solution. Furthermore, tamoxifen increased endothelial nitric oxide synthase (eNOS) phosphorylation at Ser-1177 and ICI 182,780 prevented this effect. Conclusions and Implications:The present results suggest that tamoxifen mainly induces endothelium-dependent relaxation and that endothelial nitric oxide (NO) is the primary mediator of this effect. NO-dependent responses may result from elevated [Ca 2 þ ] i in endothelial cells; an effect abolished by ICI 182,780. NO activates Na þ /K þ -ATPase in vascular smooth muscle, leading to relaxation. These results suggest that tamoxifen is able to modulate eNOS phosphorylation directly.

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“…Oestrogen also exerts ‘non‐genomic’ effects which involve steroid‐induced modulation of cytoplasmic or of cell membrane‐bound regulatory proteins such as mitogen‐activated protein kinases, phosphatidylinositol 3‐OH kinase (PI3K), ion channels, and G‐protein‐coupled receptors. Genomic effects of oestrogen include the regulation of expression of a variety of ion channels, including: down‐regulation of Cav1.2 mRNA expression and L‐type Ca 2+ channel density (Johnson et al 1997; Patterson et al 1998) and up‐regulation of large conductance Ca 2+ ‐activated K + channels (Jamali et al 2003), ATP‐sensitive K + channels (Ranki et al 2002), small conductance K + channels (Jacobson et al 2003) and K v 1.5 channels (Tsang et al 2004). Recent studies have made an important link between oestrogen and down‐regulation of A‐type currents and Kv4.3 channels in myometrial smooth muscle (Wang et al 1998; Song et al 2001; Suzuki & Takimoto, 2005).…”

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confidence: 99%

Effects of female steroid hormones on A‐type K⁺ currents in murine colon

Beckett

McCloskey

O'Kane

et al. 2006

The Journal of Physiology

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Idiopathic constipation is higher in women of reproductive age than postmenopausal women or men, suggesting that female steroid hormones influence gastrointestinal motility. How female hormones affect motility is unclear. Colonic motility is regulated by ion channels in colonic myocytes. Voltage-dependent K + channels serve to set the excitability of colonic muscles. We investigated regulation of Kv4.3 channel expression in response to acute or chronic changes in female hormones. Patch clamp experiments and quantitative PCR were used to compare outward currents and transcript expression in colonic myocytes from male, non-pregnant, pregnant and ovariectomized mice. Groups of ovariectomized mice received injections of oestrogen or progesterone to investigate the effects of hormone replacement. The capacitance of colonic myocytes from non-pregnant females was larger than in males. Net outward current density in male and ovariectomized mice was higher than in non-pregnant females and oestrogen-treated ovariectomized mice. Current densities in late pregnancy were lower than in female controls. Progesterone had no effect on outward currents. A-type currents were decreased in non-pregnant females compared with ovariectomized mice, and were further decreased by pregnancy or oestrogen replacement. Kv4.3 transcripts did not differ significantly between groups; however, expression of the potassium channel interacting protein KChIP1 was elevated in ovariectomized mice compared with female controls and oestrogen-treated ovariectomized mice. Delayed rectifier currents were not affected by oestrogen. In the mouse colon, oestrogen suppresses A-type currents, which are important for regulating excitability. These observations suggest a possible link between female hormones and altered colonic motility associated with menses, pregnancy and menopause.

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Differential regulation of K+ and Ca2+ channel gene expression by chronic treatment with estrogen and tamoxifen in rat aorta

Cited by 27 publications

References 40 publications

Raloxifene, Tamoxifen and Vascular Tone

Raloxifene, Tamoxifen and Vascular Tone

Tamoxifen dilates porcine coronary arteries: roles for nitric oxide and ouabain‐sensitive mechanisms

Effects of female steroid hormones on A‐type K⁺ currents in murine colon

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Differential regulation of K+ and Ca2+ channel gene expression by chronic treatment with estrogen and tamoxifen in rat aorta

Cited by 27 publications

References 40 publications

Raloxifene, Tamoxifen and Vascular Tone

Raloxifene, Tamoxifen and Vascular Tone

Tamoxifen dilates porcine coronary arteries: roles for nitric oxide and ouabain‐sensitive mechanisms

Effects of female steroid hormones on A‐type K+ currents in murine colon

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Effects of female steroid hormones on A‐type K⁺ currents in murine colon