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GPER regulates endothelin-dependent vascular tone and intracellular calcium
- Source :
- Life Sciences. 91(13-14):623-627
- Publication Year :
- 2012
- Publisher :
- Elsevier BV, 2012.
-
Abstract
- Aims An increase in intracellular vascular smooth muscle cell calcium concentration (VSMC [Ca2 +]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 [Ca2 +]i in cultured VSMC, we investigated whether endogenous GPER regulates ET-1-induced changes in VSMC [Ca2 +]i and constriction of intact arteries. Main methods Pressurized carotid arteries of GPER-deficient (GPER0) 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 [Ca2 +]i were recorded simultaneously. Vascular gene expression levels of ETA and ETB receptors were determined by qPCR. Key findings ET-1-dependent vasoconstriction was increased in arteries from GPER0 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 [Ca2 +]i increase, suggesting an increase in myofilament force sensitivity to [Ca2 +]i. Activation of GPER by G-1 had no effect on vasoconstriction or VSMC [Ca2 +]i responses to ET-1, and expression levels of ETA or ETB 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 Ca2 + sensitivity. This represents a potential mechanism through which GPER could contribute to protective effects of endogenous estrogen in the cardiovascular system.
- Subjects :
- Male
GPR30
Vascular smooth muscle
030204 cardiovascular system & hematology
Polymerase Chain Reaction
Muscle, Smooth, Vascular
Calcium in biology
Receptors, G-Protein-Coupled
Mice
chemistry.chemical_compound
Pharmacology, Toxicology and Pharmaceutics(all)
0302 clinical medicine
General Pharmacology, Toxicology and Pharmaceutics
Receptor
Mice, Knockout
0303 health sciences
Endothelin-1
Estradiol
General Medicine
Receptor, Endothelin A
GPER
Receptor, Endothelin B
Carotid Arteries
Receptors, Estrogen
Vascular smooth muscle cell
cardiovascular system
medicine.symptom
Fura-2
Endothelin receptor
medicine.medical_specialty
Biology
Calcium sensitivity
Article
General Biochemistry, Genetics and Molecular Biology
03 medical and health sciences
Internal medicine
medicine
Animals
Fluorescent Dyes
030304 developmental biology
Biochemistry, Genetics and Molecular Biology(all)
Endothelin 1
Mice, Inbred C57BL
Endocrinology
Gene Expression Regulation
chemistry
Vasoconstriction
Calcium
Subjects
Details
- ISSN :
- 00243205
- Volume :
- 91
- Issue :
- 13-14
- Database :
- OpenAIRE
- Journal :
- Life Sciences
- Accession number :
- edsair.doi.dedup.....9bf64ce3c24b9f11895f057ec7d529b2
- Full Text :
- https://doi.org/10.1016/j.lfs.2012.01.007