Alendronate Decreases Contractile Responses by Affecting ATP-Sensitive Potassium Channels in Human Left Internal Mammary Artery Rings


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ARUN M. Z. , REEL B. , Guzeloglu M., Albayrak G., Aykut K., Hazan E.

INTERNATIONAL JOURNAL OF PHARMACOLOGY, cilt.10, ss.501-506, 2014 (SCI İndekslerine Giren Dergi) identifier identifier

  • Cilt numarası: 10 Konu: 8
  • Basım Tarihi: 2014
  • Doi Numarası: 10.3923/ijp.2014.501.506
  • Dergi Adı: INTERNATIONAL JOURNAL OF PHARMACOLOGY
  • Sayfa Sayıları: ss.501-506

Özet

Bisphosphonates, including alendronate, are widely used for the treatment of osteoporosis, hypercalcemia and bone metastasis associated with cancer. However, recent evidence has demonstrated anti-atherosclerotic effects of bisphosphonates in animal models and atherosclerotic patients. Besides, some studies have shown that bisphosphonates change calcium homeostasis in cardiomyocytes and interfere L-type calcium channels in vascular smooth muscle cells. Therefore, in the present study it was aimed to investigate the effects of alendronate on contractile responses and ATP-sensitive potassium channels in vitro in human Left Internal Mammary Artery (LIMA). Human LIMA rings were placed into isolated organ chambers. After resting period, rings were kept for an hour in incubation medium which contains alendronate (10(-6) M) or not (control) and responses of the rings to the contractile agents were examined. The incubation of two rings was performed in the presence of glibenclamide which is ATP-sensitive potassium channel blocker (10(-6) M). Maximum contractile responses of LIMA rings to noradrenalin and serotonin decreased in the presence of alendronate. In concomitant incubation of LIMA with alendronate and glibenclamide reversed decreased contractions to noradrenalin or serotonin caused by alendronate. However, neither alendronate nor glibenclamide changed sensitivity to noradrenaline or serotonin. The present findings point out that alendronate may change intracellular calcium dynamics in human LIMA, due to the activation of ATP-sensitive potassium channels which have an important role on cardiovascular system.