Estrogen and Tamoxifen Modulate Cerebrovascular Tone in Ovariectomized Female Rats

Tsang, Suk Ying; Yao, Xiaoqiang; Chan, Franky L.; Wong, Chun Kit; Chen, Zhenyu; Laher, Ismail; Huang, Yü

doi:10.1161/01.hyp.0000131659.27081.19

Cited by 34 publications

(24 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Similarly, the ability of TAM to potentiate vasoconstrictor effects in the mesenteric vasculature appear to be completely reversed in that BP actually decreased. Conversely, other work has shown TAM and estrogen to have no significant effects on BP in an ovariectomized rat model (38). In contrast to our study, that experiment was performed using a subcutaneous pellet to administer the hormone instead of gavage treatment, which may account for the discrepancies with our study.…”

Section: Discussioncontrasting

confidence: 85%

Effects of estrogens and selective estrogen receptor modulators on vascular reactivity in the perfused mesenteric vascular bed

Mark¹,

Tatchum-Talom²,

Martin³

et al. 2007

American Journal of Physiology-Regulatory, Integrative and Comp

View full text Add to dashboard Cite

Mark CJ, Tatchum-Talom R, Martin DS, Eyster KM. Effects of estrogens and selective estrogen receptor modulators on vascular reactivity in the perfused mesenteric vascular bed. Am J Physiol Regul Integr Comp Physiol 293: R1969-R1975, 2007. First published September 19, 2007; doi:10.1152/ajpregu.00260.2007.-Estrogens and selective estrogen receptor modulators (SERMs), such as raloxifene (RAL) and tamoxifen (TAM), acutely relax arteries, but the long-term effects of estrogens and SERMs on vascular reactivity in the mesenteric vasculature have not been well defined. In this study, we used an isolated, perfused mesenteric vascular bed technique to investigate the effect of chronic treatment of estrogens and SERMs on vascular reactivity of the mesenteric bed. Ovariectomized female SpragueDawley rats were treated by gavage with vehicle (control, 2-hydroxypropyl-␤-cyclodextrin), ethinyl estradiol, estradiol benzoate, equilin (EQ), TAM, or RAL for 3 wk. EQ and TAM increased vasoconstriction in response to all three vasoconstrictors tested (KCl, norepinephrine, and 5-HT). Ethinyl estradiol increased vasoconstriction in response to KCl and 5-HT, whereas responses to estradiol benzoate and RAL were less consistent. Only EQ (134 Ϯ 4 mmHg) and TAM (104 Ϯ 4 mmHg) changed mean arterial blood pressure compared with control (117 Ϯ 4 mmHg). These data demonstrate that 3-wk gavage treatment with estrogens and SERMs affects vascular reactivity in the mesenteric vascular bed. However, the three formulations of estrogen did not produce equivalent effects, and the effects of the SERMs were different from those of the estrogens. equilin; ethinyl estradiol; estradiol benzoate; tamoxifen; raloxifene CARDIOVASCULAR DISEASE (CVD) is one of the most common diseases in the industrialized world and is a major cause of human death (10). The incidence of CVDs, such as hypertension and atherosclerosis, is greater in men than in premenopausal women (13). Among women, the incidence of CVD is greater in postmenopausal women than premenopausal women (39). The loss of estrogen at the menopause is hypothesized to underlie the epidemiological link between menopause and increased cardiovascular risk. Thus it is important to continue to gain a better understanding of the action of estrogen on the vascular system. Alterations in vascular tone play a major role in the control of blood pressure (BP) and thereby the incidence of hypertension and CVD. 17␤-Estradiol has been shown to act acutely as a direct vasodilator (27). Conversely, Li and Stallone have shown that chronic 3-wk treatment with estrogen potentiated the contractile responses of the female rat aorta to vasopressin (24a). For this investigation, we chose a chronic 3-wk treatment with three formulations of estrogen and two selective estrogen receptor modulators (SERMs). The estrogens chosen for this study are among the most routinely used for research and therapeutic treatment. Ethinyl estradiol (EE) is used orally, either alone or with a progestin, in oral contraceptives (43). Equilin (EQ) is an...

show abstract

Section: Discussioncontrasting

confidence: 85%

Effects of estrogens and selective estrogen receptor modulators on vascular reactivity in the perfused mesenteric vascular bed

Mark¹,

Tatchum-Talom²,

Martin³

et al. 2007

American Journal of Physiology-Regulatory, Integrative and Comp

View full text Add to dashboard Cite

show abstract

“…Other studies have demonstrated that tamoxifen reduces the mRNA expression of the α 1C subunit of the L-type Ca 2+ channel in the absence of estrogen and augments the mRNA expression of voltage-dependent potassium channels (K v ), thus possibly contributing to the vasodilatory response (38).…”

Section: Discussionmentioning

confidence: 99%

Effect of tamoxifen on the coronary vascular reactivity of spontaneously hypertensive female rats

Borgo

Lopes

Gouvêa

et al. 2011

Braz J Med Biol Res

View full text Add to dashboard Cite

“…2,[15][16][17] Vascular contraction is greater in blood vessels of intact male than intact female rats, not different between castrated and intact males, but greater in ovariectomized (OVX) than intact females. 18,19 Also, estrogen replacement in OVX female rats restores the vascular contraction to its level in intact females, 3 suggesting that the gender differences in vascular contraction may involve direct effects of estrogen on specific hormone receptors in the vasculature.…”

Section: Gender Differences In Vascular Reactivitymentioning

confidence: 99%

“…1,2 Experimental and initial clinical data have suggested that hormone replacement therapy (HRT) may reduce cardiovascular disease in postmenopausal women. [3][4][5][6] On the other hand, reports from Heart and Estrogen-Progestin Replacement Study (HERS), HERS2, and Women's Health Initiative (WHI) clinical trials did not support vascular benefits of HRT in postmenopausal women. 1,7,8 However, the lack of beneficial effects of HRT could be explained by the small number of subjects studied and that subjects were mainly elderly women.…”

mentioning

confidence: 99%

Sex Hormones as Potential Modulators of Vascular Function in Hypertension

Khalil

2005

Hypertension

160

View full text Add to dashboard Cite

Abstract-The greater incidence of hypertension in men and postmenopausal women compared with premenopausal women has suggested gender differences in vascular function. Vascular effects of the female sex hormones estrogen and progesterone and the male hormone testosterone have been described. Sex steroid receptors have been identified in vascular endothelium and smooth muscle. Interaction of sex hormones with cytosolic/nuclear receptors initiates long-term genomic effects that stimulate endothelial cell growth but inhibit smooth muscle proliferation. Activation of sex hormone receptors on the plasma membrane triggers nongenomic effects that stimulate endothelium-dependent vascular relaxation via NO-cGMP, prostacyclin-cAMP, and hyperpolarization pathways. Sex hormones also cause endothelium-independent inhibition of vascular smooth muscle contraction, [Ca 2ϩ ] i , and protein kinase C. These vasorelaxant/vasodilator effects suggested vascular benefits of hormone replacement therapy (HRT) during natural and surgically induced deficiencies of gonadal hormones. Although some clinical trials showed minimal benefits of HRT in postmenopausal hypertension, the lack of effect should not be generalized because it could be related to the type/dose of sex hormone, subjects' age, and other cardiovascular conditions. The prospect of HRT relies on continued investigation of the molecular mechanisms underlying the vascular effects of sex hormones and identification of compounds that specifically target the vascular sex hormone receptors. Naturally occurring hormones and phytoestrogens may be more beneficial HRT than synthesized compounds. Also, the type/dose, time of initiation, and duration of HRT should be customized depending on the subject's age and preexisting cardiovascular condition, and thereby enhance the outlook of sex hormones as potential modulators of vascular function in hypertension.

show abstract

Estrogen and Tamoxifen Modulate Cerebrovascular Tone in Ovariectomized Female Rats

Cited by 34 publications

References 39 publications

Effects of estrogens and selective estrogen receptor modulators on vascular reactivity in the perfused mesenteric vascular bed

Effects of estrogens and selective estrogen receptor modulators on vascular reactivity in the perfused mesenteric vascular bed

Effect of tamoxifen on the coronary vascular reactivity of spontaneously hypertensive female rats

Sex Hormones as Potential Modulators of Vascular Function in Hypertension

Contact Info

Product

Resources

About