Program

PO2-3-14

INVOLVEMENT OF ATP-SENSITIVE POTASSIUM CHANNELS IN PINACIDIL EFFECTS ON THE ISOLATED BYPASS GRAFTS FROM PATIENTS WITH TYPE-2 DIABETES MELLITUS

[Speaker] Jovana Rajkovic:1
[Co-author] Miodrag Peric:2, Jelena Stanisic:3, Jelena Rakocevic:4, Radmila Novakovic:1, Vladimir Djokic:1, Milica Labudovic-Borovic:4, Snezana Tepavcevic:3, Helmut Heinle:5, Ljiljana Gojkovic-Bukarica:1
1:Institute for Pharmacology, Clinical Pharmacology and Toxicology, Medical Faculty, Serbia, 2:Dedinje Cardiovascular Institute, Serbia, 3:Laboratory for Molecular Biology and Endocrinology, Vinca Institute of Nuclear Sciences, Serbia, 4:Institute of Histology and Embryology, Medical Faculty, Serbia, 5:Institute of Physiology, University of Tuebingen, Germany

The bypass grafts obtained from the diabetic patients have a tendency to develop vasospasm. Inhibition of vasospasm could be achieved by potassium channel openers (PCOs), drugs that activate ATP-sensitive K+ (KATP) channels in the vascular smooth muscle. It is a little known about the role of these channels in PCO effects on the blood vessels of patients with type-2 diabetes mellitus (T2DM). Thus, the aim of our study was to investigate the contribution of KATP channels in the effect of the PCO, pinacidil, on the bypass grafts obtained from patients with T2DM.
The rings of human saphenous vein (HSV) and internal mammary artery (HIMA), without endothelium, obtained from patients with T2DM were mounted in an organ bath system and isometric tension was being recorded. Pinacidil was used for relaxation of HSV and HIMA precontracted with phenylephrine (0.1 mM) and 5-hydroxytryptamine (0.1 mM). Western blot and immunohistochemistry have been using for detection of expression of KATP subunits (Kir6.1 and SUR-2B) on the grafts obtained from patients with/without T2DM.
Pinacidil (0.01 - 100 microM) produced a concentration-dependent relaxation of HSV (pD2=5.9, n=17) and HIMA (pD2=5.9, n=16). Glibenclamide (GLB, 10 microM), a highly selective blocker of KATP channels, antagonize the relaxation induced by pinacidil on HSV from patients with T2DM (pD2=5.1, n=7, p < 0.05). GLB did not significantly antagonize the effect of pinacidil on the HIMA (pD2=5.7, n=6, p > 0.05). Western blot and immunohistochemistry shown that Kir6.1 and SUR-2B subunits were expressed in the smooth muscle of both grafts from patients with/without T2DM. However, we only detected lower expression of SUR-2B subunit in the smooth muscle of HSV obtained from patients with T2DM (p < 0.05).
Pinacidil produces endothelium-independent relaxation of HSV and HIMA obtained from diabetic patients. According to the pharmacological and molecular analysis, it seems that the contribution of smooth muscle KATP channels in relaxant effects of pinacidil was more significant on the HSV than on the HIMA from patients with T2DM.
This work was supported by scientific research grant no. TR31020 from the Ministry of Education, Science and Technological Development, Republic of Serbia.

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