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GPER1 agonist improves cerebral microvascular function after hypoxia/reoxygenation injury in male and female rats
Author(s) -
Murata Takahiro,
Dietrich Hans H.,
Horiuchi Tetsuyoshi,
Hongo Kazuhiro,
Dacey Ralph G.
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.700.6
Subject(s) - agonist , vasomotor , endocrinology , hypoxia (environmental) , vasodilation , nitric oxide , adenosine , medicine , chemistry , ischemia , estrogen , endothelium , receptor , oxygen , organic chemistry
Estrogen is a known neuro‐ and vaso‐protective agent in experimental cerebral ischemia. Recently, a novel G protein‐coupled estrogen receptor 1 (GPER1) has been identified. We investigated the mechanism of GPER1 mediated vasoreactivity and also its vasoprotective effect after hypoxia/reoxygenation (H/RO) injury. Rat cerebral penetrating arterioles from both genders were isolated, cannulated and pressurized. Vessel diameters were measured. To investigate vasomotor mechanism of the GPER1 agonist (G‐1), several inhibitors were tested. Ischemia/reperfusion (I/R) injury was simulated using H/RO. Vasomotor responses to adenosine tri‐phophate (ATP) after H/RO were measured with or without G‐1. G‐1 produced a vasodilatory response, which was partially dependent on endothelium‐derived nitric oxide (NO) but not arachidonic acid cascades and endothelial hyperpolarization factor. G‐1 treatment after H/RO injury fully restored arteriolar dilation to ATP compared to controls. In conclusion, GPER1 agonist elicited dilation, which partially caused by endothelial NO pathway and induced by direct relaxation of smooth muscle cells. Further, GPER1 agonist restored vessel function of arterioles after H/RO injury and may play an important role in estrogen fs ability to protect the cerebrovasculature against I/R injury. Support: NIH P01 NS32636, NIH R01 HL041250, NIH R01 NS30555, and KAKENHI 24890079.