Volume 25, Issue S1 p. 809.4-809.4
Pharmacology/Experimental Therapeutics
Free Access

Involvement of AMPK in the Beneficial Vascular Effect of a Non-selective PPAR Activator in Aorta of Spontaneously Hypertensive Rats

Chen Qu

Chen Qu

Department of Pharmacology and Pharmacy, The University of Hong Kong, Hong Kong, Hong Kong

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Susan W.S. Leung

Susan W.S. Leung

Department of Pharmacology and Pharmacy, The University of Hong Kong, Hong Kong, Hong Kong

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Paul M Vanhoutte

Paul M Vanhoutte

Department of Pharmacology and Pharmacy, The University of Hong Kong, Hong Kong, Hong Kong

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Ricky Y.K. Man

Ricky Y.K. Man

Department of Pharmacology and Pharmacy, The University of Hong Kong, Hong Kong, Hong Kong

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Abstract

Wy14643 is an 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 (SHR) was recorded. Protein expressions of eNOS, phosphorylated eNOS, AMP-activated protein kinase (AMPK), phosphorylated AMPK were analyzed by Western blotting. 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 (AMPK inhibitor) reduced Wy14643-induced relaxations to the same extent as L-NAME. The phosphatidyl-inositol-3kinase-Akt inhibitor, wortamannin, had no effect on relaxation. Phosphorylated eNOS and phosphorylated AMPK expression were both increased in the presence of Wy14643 and fenofibrate. Our data suggests that PPARα activation induces nitric oxide-mediated relaxation through activation of AMPK. This relaxing effect is more prominent with Wy14643 than fenofibrate. It appears that Wy14643 with additional PPARγ effect may provide better protection against vascular dysfunction in SHR.