The G protein-coupled estrogen receptor GPER1/GPR30 is implicated in blood pressure regulation but the mechanisms are not identified. Here, we hypothesize that GPER1 controls blood pressure by regulating vascular smooth muscle cell Ca2+ handling. Treatment with the GPER1 agonist G-1 (in the μM concentration range) acutely reduced spontaneous and synchronous Ca2+ spike activity in A7r5 vascular smooth muscle cells expressing mRNA for GPER1. Furthermore, G-1 (1 μM) attenuated the thromboxane A2 analogue U46619-stimulated Ca2+ spike activity but had no effect on the U46619-induced increase in the basal level of Ca2+. The voltage-sensitive L-type Ca2+ channel blocker nifedipine (100 nM) reduced Ca2+ spike activity similar to G-1. Pharmacological, but not physiological, concentrations of the estrogen 17β-estradiol reduced Ca2+ spike activity. The GPER1 antagonist G-15 blocked G-1-induced downregulation of Ca2+ spike activity, supporting a GPER1-dependent mechanism. G-1 (1 μM) and nifedipine (100 nM) attenuated the 30-mM KCl-evoked rise in intracellular Ca2+ concentration, suggesting that G-1 blocks inflow of Ca2+ via voltage-sensitive Ca2+ channels. In conclusion, we demonstrate that the GPER1 agonist G-1 regulates vascular smooth muscle cell Ca2+ handling by lowering Ca2+ spike activity, suggesting a role for this mechanism in GPER1-mediated control of blood pressure.
Bibliographical notePublisher Copyright:
© 2013 S. Karger AG, Basel.
- Calcium spikes
- Estrogen receptor
- Vascular smooth muscle cells