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Life Sci. 2012 Oct 15;91(13-14):623-7. doi: 10.1016/j.lfs.2012.01.007. Epub 2012 Feb 2.

GPER regulates endothelin-dependent vascular tone and intracellular calcium.

Author information

1
Department of Cell Biology and Physiology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, United States.

Abstract

AIMS:

An increase in intracellular vascular smooth muscle cell calcium concentration (VSMC [Ca(2+)](i)) is essential for endothelin-1 (ET-1)-induced vasoconstriction. Based on previous findings that activation of the G protein-coupled estrogen receptor (GPER) inhibits vasoconstriction in response to ET-1 and regulates [Ca(2+)](i) in cultured VSMC, we investigated whether endogenous GPER regulates ET-1-induced changes in VSMC [Ca(2+)](i) and constriction of intact arteries.

MAIN METHODS:

Pressurized carotid arteries of GPER-deficient (GPER(0)) and wildtype (WT) mice were loaded with the calcium indicator fura 2-AM. Arteries were stimulated with the GPER-selective agonist G-1 or solvent followed by exposure to ET-1. Changes in arterial diameter and VSMC [Ca(2+)](i) were recorded simultaneously. Vascular gene expression levels of ET(A) and ET(B) receptors were determined by qPCR.

KEY FINDINGS:

ET-1-dependent vasoconstriction was increased in arteries from GPER(0) compared to arteries from WT mice. Despite the more potent vasoconstriction to ET-1, GPER deficiency was associated with a marked reduction in the ET-1-stimulated VSMC [Ca(2+)](i) increase, suggesting an increase in myofilament force sensitivity to [Ca(2+)](i). Activation of GPER by G-1 had no effect on vasoconstriction or VSMC [Ca(2+)](i) responses to ET-1, and expression levels of ET(A) or ET(B) receptor were unaffected by GPER deficiency.

SIGNIFICANCE:

These results demonstrate that endogenous GPER inhibits ET-1-induced vasoconstriction, an effect that may be associated with reduced VSMC Ca(2+) sensitivity. This represents a potential mechanism through which GPER could contribute to protective effects of endogenous estrogen in the cardiovascular system.

PMID:
22326502
PMCID:
PMC3355219
DOI:
10.1016/j.lfs.2012.01.007
[Indexed for MEDLINE]
Free PMC Article

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