17 beta-Estradiol attenuates voltage-dependent Ca2+ currents in A7r5 vascular smooth muscle cell line

Abstract

Previous studies have shown that 17 beta-estradiol (beta-E2) has a direct acute inhibitory effect on vascular smooth muscle (VSM) contraction. To investigate the mechanisms underlying this phenomenon, we utilized whole cell patch-clamping techniques to study effects of beta-E2 on voltage-dependent Ca2+ channels in cultured VSM cells (VSMC). T- and L-type Ca2+ currents were characterized with ramp and pulse protocols in A7r5 cultured VSMC. T-type current, inactivated in < 100 ms, was reduced by Ba2+ and was comparatively little affected by isradipine. L-type current required higher voltages to activate, inactivated slowly, was greatly increased by Ba2+, and could be completely inhibited by 5 microM isradipine. beta-E2 (10 microM) significantly reduced peak L-type Ba2+ current and T-type Ca2+ current within 1-2 min, whereas alpha E2 (a hormonally inactive isomer of estradiol) caused significantly less reduction in both types of current. Vehicle (0.1% ethanol) had no significant effect on either current. The inhibitory effect of beta-E2 on voltage-dependent Ca2+ currents may contribute to previously demonstrated beta-E2 attenuation of VSM contraction.

Antagonistic Effects of 17β-Estradiol, Progesterone, and Testosterone on Ca 2+ Entry Mechanisms of Coronary Vasoconstriction

“…To our knowledge, 1 study has shown that estrogen blocks voltage-gated Ca 2ϩ channels in cultured A7r5 cells. 31 Although the Ca 2ϩ permeability through voltage-gated channels may be different in cultured cells, our present results in coronary smooth muscle are still consistent with the findings of this report and should represent an important area for future electrophysiology investigations. Finally, we investigated whether the sex hormones inhibit PGF 2␣ -and depolarization-induced coronary smooth muscle contractions by inhibiting the same Ca 2ϩ -entry pathway.…”

Sex hormone modulation of serotonin-induced coronary vasodilation in isolated heart

“…Several studies have demonstrated that the incidence of cardiovascular diseases is higher in men compared with premenopausal women. This difference also exists in agonist-induced vascular responses of experimental animals (2)(3)(4). Although little is known about the mechanisms underlying this phenomenon, epidemiological and experimental evidence indicates that female sex hormones, in particular 17ß-estradiol, have protective effects against cardiovascular diseases (5,6) because estrogen replacement therapy reduces the incidence of coronary artery disease (7,8).…”

Human vascular smooth muscle cells express an estrogen receptor isoform

“…However, systemic effects of estrogens do not account fo ~" the majority of the observed atheroprotective effects of E2 [2.3,15,16]. In an effort to reveal additional pathways that may mediate the atheroprotective effects of E2, direct effects of E2 ol ~, vascular cells are currently being investigated (reviewed in [1 '] Direct effects of E2 on vascular cell function were first suggested decades ago [7,18] and have since been shown both in whole animal and in vitro studies [10,[19][20][21][22][23][24][25][26][27][28][29][30]. However, the signaling pathways involved in the direct effects of E2 on vascular cells are not yet characterized.…”