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Beneficial Vascular Effect of A Non‐selective PPAR Activator In Aorta of Spontaneously Hypertensive Rats
Author(s) -
Qu Chen,
Leung Susan W.S.,
Vanhoutte Paul M.,
Man Ricky Y.K.
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.955.10
Subject(s) - activator (genetics) , ampk , rosiglitazone , nitric oxide , fenofibrate , endocrinology , medicine , peroxisome proliferator activated receptor , receptor , chemistry , pharmacology , protein kinase a , kinase , biochemistry
Wy14643 is a potent activator of peroxisome proliferator‐activated receptor (PPAR) α and γ. The present study aimed to determine whether or not Wy14643 improved endothelial dysfunction in hypertension, and if so, the mechanism involved. Isometric tension in isolated thoracic aortic rings of spontaneously hypertensive rats was recorded. Wy14643 caused greater relaxations than fenofibrate (PPARα activator) or rosiglitazone (PPARγ activator). L‐NAME (nitric oxide synthase inhibitor) and ODQ (soluble guanylyl cyclase inhibitor) alone and in combination inhibited these relaxations to the same extent. Compound C (AMP‐activated protein kinase (AMPK) inhibitor) reduced Wy14643‐induced relaxations to the same extent as L‐NAME. Endothelium‐dependent contractions evoked by acetylcholine in the presence of L‐NAME were reduced by Wy14643, fenofibrate but not rosiglitazone. Moreover, Wy14643 and fenofibrate inhibited acetylcholine‐induced prostanoids release to the same extent. Our data suggests that the three PPAR activators induce nitric oxide‐mediated relaxation through activation of AMPK. This relaxing effect is more prominent with Wy14643. Together with the ability to reduce the release of endothelium‐dependent contracting factor, it appears that Wy14643 produces better protection against vascular diseases in spontaneous hypertension.