QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: jpet.106.100958v1 318/1/312    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Kinoshita, H. Articles by Hatano, Y. Search for Related Content PubMed PubMed Citation Articles by Kinoshita, H. Articles by Hatano, Y.

CARDIOVASCULAR

Synthetic Peroxisome Proliferator-Activated Receptor- Agonists Restore Impaired Vasorelaxation via ATP-Sensitive K⁺ Channels by High Glucose

Department of Anesthesiology, Wakayama Medical University, Wakayama, Japan (H.K., K.N., Y.K., M.D., Y.H.); Department of Anesthesia, Hiroshima General Hospital, Hiroshima, Japan (T.A.); Department of Anesthesia, Japanese Red Cross Society Wakayama Medical Center, Wakayama, Japan (H.I.); and Department of Anesthesiology and Critical Care, Division of Clinical Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan (O.Y.)

The present study was designed to examine whether in the human artery, synthetic peroxisome proliferator-activated receptor (PPAR)- agonists restore vasorelaxation as well as hyperpolarization via ATP-sensitive K⁺ channels impaired by the high concentration of D-glucose and whether the restoration may be mediated by the antioxidant capacity of these agents. The isometric force and membrane potential of human omental arteries without endothelium were recorded. The production rate of superoxide was evaluated using a superoxide-generating system with xanthine-xanthine oxidase in the absence of smooth muscle cells. Glibenclamide abolished vasorelaxation and hyperpolarization in response to levcromakalim. Addition of D-glucose (20 mM) but not L-glucose (20 mM) reduced this vasorelaxation and hyperpolarization. Synthetic PPAR- agonists (troglitazone and rosiglitazone) and/or an inhibitor of superoxide generation (4,5-dihydroxy-1,3-benzene-disulfonic acid, Tiron), but not a PPAR- agonist (fenofibrate), restored vasorelaxation and hyperpolarization in response to levcromakalim in arteries treated with D-glucose. Troglitazone and rosiglitazone, but not fenofibrate, decreased the production rate of superoxide without affecting uric acid generation. These findings suggest that synthetic PPAR- agonists recover the function of ATP-sensitive K⁺ channels reduced by the high concentration of glucose in human vascular smooth muscle cells and that the effect of these agonists may be mediated in part by their antioxidant capacity.

Address correspondence to: Dr. Hiroyuki Kinoshita, Department of Anesthesiology, Wakayama Medical University, 811-1 Kimiidera, Wakayama 641-0012, Japan. E-mail: hkinoshi{at}pd5.so-net.ne.jp