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PPARα agonists acutely dilate the mouse middle cerebral artery
Author(s) -
Parelkar Nikhil K,
Badr Mostafa Z,
Andresen Jon
Publication year - 2010
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.24.1_supplement.979.6
Subject(s) - myograph , peroxisome proliferator activated receptor , vasodilation , chemistry , cerebral circulation , endocrinology , cerebral arteries , medicine , receptor , gemfibrozil , pharmacology , cholesterol
Peroxisome proliferator activated receptors (PPARs) are nuclear hormone receptors that are mainly involved in lipid metabolism. Studies investigating the role of PPARs have mainly focused on cardioprotective and lipid lowering effects of PPAR agonists. The purpose of this study was to investigate possible acute effects of the PPARα agonists gemfibrozil, WY14643, and GW7647 in pressurized and perfused mouse middle cerebral arteries (MCAs). MCAs were mounted between two glass capillary pipettes in a myograph containing Krebs buffer heated to 37°C. Arteries were pressurized to 75 mm Hg and perfused with Krebs. In MCAs preconstricted with phenylephrine (10 −5 M), gemfibrozil was a weak dilator achieving a peak dilation of only 27.8%. The more selective PPARα agonists WY14643 and GW7647, however, maximally dilated preconstricted MCAs in a concentration‐dependant manner. The highly PPARα specific compound GW7647 was 50‐fold more potent than WY14643. GW7647 had logEC50=‐5.86±0.14 whereas, WY14643 had logEC50=−4.02±0.06. Neither endothelial denudation nor nitric oxide synthase and cycloxygenase inhibition altered the dilation to GW7647. This study demonstrates that PPARα agonists acutely dilate cerebral arteries in vitro and suggests a higher vasodilatory capacity with greater PPARα selectivity. This research was supported by an AHA SDG (0735053N) and UMKC start‐up funds.