GPER regulates endothelin-dependent vascular tone and intracellular calcium.
Life Sci
; 91(13-14): 623-7, 2012 Oct 15.
Article
en En
| MEDLINE
| ID: mdl-22326502
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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Calcio
/
Endotelina-1
/
Receptores Acoplados a Proteínas G
/
Músculo Liso Vascular
Límite:
Animals
Idioma:
En
Revista:
Life Sci
Año:
2012
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Países Bajos