The role of potassium channels in the effect of resveratrol on the isolated renal artery of diabetic rats

[Speaker] Ljiljana Gojkovic-Bukarica:1
[Co-author] Jasmina Markovic Lipkovski:2, Vladimir Djokic:1, Jovana Rajkovic:1, Helmut Heinle:3, Sanja Cirovic:2, Radmila Novakovic:1
1:Institute of Pharmacology, Clinical Pharmacology and Toxicology, Medical faculty, University of Belgrade, Serbia, 2:Institute of Pathology, Faculty of Medicine, University of Belgrade, Serbia, 3:Institute of Physiology, University of Tuebingen, Germany

Background: Recently it has been documented that wine polyphenol, resveratrol improved metabolic parameters in animal models of diabetes. However, the effect of resveratrol on vasculature of diabetic animal is not well defined. Thus, the aims of our study were to investigate the effect of resveratrol on the vascular tone of rat renal artery (RA) and to defined the role of nitric oxide (NO) and a voltage-sensitive potassium (Kv) channels in its effect.
Methods: Rings of RA were isolated from normal and diabetic Wistar rats in which diabetes was induced by five-weeks alloxan treatment. Resveratrol was added to the bath cumulatively. In order to test the endothelium-dependent effect of resveratrol, a specific inhibitor of NO synthase, L-NAME was used. In order to test the endothelium-independent effect of resveratrol, blockers of different Kv channels were used: 4-aminopyridine, phrixotoxin, charybdotoxin and margatoxin.The presence and distribution of different Kv channel was determined by immunohistochemical staining with specific antibodies. Results: Resveratrol exerts potent NO-dependent relaxation of normal RA and NO-independent relaxation of RA of diabetic rats (EC50 were 8 and 50 microM, respectively). A nonselective blocker of Kv channels,4-aminopyridine partly inhibited the relaxation of RA of normal as well as of diabetic rats. A selective antagonist of Kv4.2 channels, phrixotoxin antagonized the effect of resveratrol on the RA of normal rats. Margatoxin, a selective antagonist of Kv1.3 channels, completely antagonized the resveratrol-induced relaxation of RA of diabetic rats. Immunohistochemical staining showed the protein expression of KV1.1-6 and Kv4.2. channels in the endothelium of healthy vessels and in the media of RA of diabetic and non-diabetic rats. In the endothelium of RA of diabetic rats, Kv1.3 channels were presented only. The Kv2.1 channel were not expressed nor in RA of diabetic neither in RA of normal rats. Conclusions: Reservatrol relaxed RA of normal rats in NO-dependent and independent manner, probably by an interaction with Kv4.2 channels. However, resveratrol relax RA of diabetic rats by an interaction with margatoxin-sensitive Kv1.3 channels.

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