In:
Journal of Vascular Research, S. Karger AG, Vol. 50, No. 5 ( 2013), p. 421-429
Abstract:
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 Ca 〈 sup 〉 2+ 〈 /sup 〉 handling. Treatment with the GPER1 agonist G-1 (in the µ 〈 smlcap 〉 M 〈 /smlcap 〉 concentration range) acutely reduced spontaneous and synchronous Ca 〈 sup 〉 2+ 〈 /sup 〉 spike activity in A7r5 vascular smooth muscle cells expressing mRNA for GPER1. Furthermore, G-1 (1 µ 〈 smlcap 〉 M 〈 /smlcap 〉 ) attenuated the thromboxane A 〈 sub 〉 2 〈 /sub 〉 analogue U46619-stimulated Ca 〈 sup 〉 2+ 〈 /sup 〉 spike activity but had no effect on the U46619-induced increase in the basal level of Ca 〈 sup 〉 2+ 〈 /sup 〉 . The voltage-sensitive L-type Ca 〈 sup 〉 2+ 〈 /sup 〉 channel blocker nifedipine (100 n 〈 smlcap 〉 M 〈 /smlcap 〉 ) reduced Ca 〈 sup 〉 2+ 〈 /sup 〉 spike activity similar to G-1. Pharmacological, but not physiological, concentrations of the estrogen 17β-estradiol reduced Ca 〈 sup 〉 2+ 〈 /sup 〉 spike activity. The GPER1 antagonist G-15 blocked G-1-induced downregulation of Ca 〈 sup 〉 2+ 〈 /sup 〉 spike activity, supporting a GPER1-dependent mechanism. G-1 (1 µ 〈 smlcap 〉 M 〈 /smlcap 〉 ) and nifedipine (100 n 〈 smlcap 〉 M 〈 /smlcap 〉 ) attenuated the 30-m 〈 smlcap 〉 M 〈 /smlcap 〉 KCl-evoked rise in intracellular Ca 〈 sup 〉 2+ 〈 /sup 〉 concentration, suggesting that G-1 blocks inflow of Ca 〈 sup 〉 2+ 〈 /sup 〉 via voltage-sensitive Ca 〈 sup 〉 2+ 〈 /sup 〉 channels. In conclusion, we demonstrate that the GPER1 agonist G-1 regulates vascular smooth muscle cell Ca 〈 sup 〉 2+ 〈 /sup 〉 handling by lowering Ca 〈 sup 〉 2+ 〈 /sup 〉 spike activity, suggesting a role for this mechanism in GPER1-mediated control of blood pressure.
Type of Medium:
Online Resource
ISSN:
1018-1172
,
1423-0135
Language:
English
Publisher:
S. Karger AG
Publication Date:
2013
detail.hit.zdb_id:
1482726-8
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