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GPR30 Attenuates Functional AT1 Receptor Expression in Rat Mesenteric Smooth Muscle Cells
Author(s) -
Lindsey Sarah H.,
Bhat Manjunatha,
Aileru Azeez,
Chappell Mark
Publication year - 2011
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.25.1_supplement.1088.8
Subject(s) - angiotensin ii receptor type 1 , receptor , microbiology and biotechnology , gper , medicine , chemistry , endocrinology , biology , angiotensin ii , estrogen receptor , cancer , breast cancer
Our studies in the congenic mRen2. Lewis strain, an angiotensin II (Ang II) and estrogen dependent model of hypertension, demonstrate that chronic activation of estrogen receptor GPR30 markedly reduces blood pressure and attenuates expression of the vascular ACE‐AT1 receptor axis. The objective of the current study was to establish GPR30 expression in mesenteric smooth muscle cells (MSMC) and determine whether GPR30 influences AT1 receptor expression. Formalin‐fixed mesenteric vessels (<200 μm) from the mRen2. Lewis female were immunopositive for GPR30 in the media and intima. Cultured MSMCs also expressed GPR30 in addition to angiotensinogen, ACE2, and the AT1 receptor. Ang II receptor subtypes were characterized using 125I‐Sarthran binding and specific antagonists for the AT1 receptor (losartan) and the AT2 receptor (PD‐123319). The majority of binding (~83%) was attributed to the AT1 receptor, with significantly less binding (~16%) at the AT2 receptor. Treatment with the GPR30 agonist G‐1 (10–100 nM) significantly decreased Ang II receptor binding (60–75%; *P < 0.001). Fura‐2 Ca2+ imaging revealed that G‐1 treatment blunted the Ang II‐induced increase in intracellular Ca2+. We conclude that GPR30 receptors may directly attenuate functional AT1 receptor expression thereby contributing to the beneficial actions of estrogen in the vasculature. Funding: AHA 0825515, 10BGIA3080005, HL56973, HL51952.