The Effects of 17�-Oestradiol on Increased a₁-Adrenergic Vascular Reactivity Induced by Prolonged Ovarian Hormone Deprivation: The Role of Voltage-Dependent L-type Ca²⁺Channels

Abstract

The present study investigated the hypothesis that the duration of ovarian hormone deprivation before reintroduction of oestrogen affects the role of oestrogen as a mediator of the contractile function of α₁-adrenergic receptors. Rats underwent ovariectomy (OVX) or were sham-operated, and the OVX rats were treated with vehicle (corn oil) or 17β-oestradiol (E₂) for 5 days either 10, 28 or 60 days after OVX. The OVX increased phenylephrine- and Ca²⁺-induced contractions. Interestingly, the phenylephrine-induced contractions were increased at each of the three time points, whereas the Ca²⁺-induced contractions were only increased in the 60-day group. E₂ had biphasic effects on phenylephrine- and Ca²⁺-induced contractility. Indeed, E₂ increased contractions in the 10-day group and diminished contractions in the other groups (the increased contractions were avoided by verapamil). These results indicate that E₂ controls α₁-adrenergic receptor-mediated contractility through effects on L-type Ca²⁺ channels in a way that depends on the timing in which the treatment with E₂ is initiated.

Timing Matters: Effects of Early and Late Estrogen Replacement Therapy on Glucose Metabolism and Vascular Reactivity in Ovariectomized Aged Wistar Rats

“…Our results showed an increase in Ca +2 channel reactivity in aortic rings at 10- but not 20-week postovariectomy. In agreement with our results, Valencia-Hernández et al demonstrated that Ca 2+ vascular reactivity in ovariectomized female rats depends on the postovariectomy time, finding an increase in Ca 2+ response at 8 weeks, but not at 1 or 3 weeks after the surgery [78]. Kim and Yang also found an increase in K Ca channel conductance two weeks after ovariectomy [79].…”

Sex differences in the vascular function and related mechanisms: role of 17β-estradiol

“…On the other hand, 17␤E-mediated regulation of VGCC also depends on the timing of initiation of 17␤E treatment. Animals treated with 17␤E for 10, 28, and 60 days after OVX increased VGCC-mediated contraction in the 10-day treatment group, whereas there was no change in VGCC-mediated contraction with 28-and 60-day treatment, highlighting the importance of the timing hypothesis (248). Overall, these studies suggest that 17␤E, via genomic and nongenomic actions, can regulate VGCC ␣and ␤-subunit expression and function and, furthermore, that these actions depend on the time of initiation of 17␤E treatment.…”