Role of Calcium-Activated Potassium Channels with Small Conductance in Bradykinin-Induced Vasodilation of Porcine Retinal Arterioles

PURPOSE. Endothelial dysfunction and impaired vasodilation may be involved in the pathogenesis of retinal vascular diseases. In the present study, the mechanisms underlying bradykinin vasodilation were examined and whether calcium-activated potassium channels of small (SKCa) and intermediate (IKCa) conductance are involved in regulation of endothelium-dependent vasodilation in retinal arterioles was investigated. METHODS. Porcine retinal arterioles (diameter similar to 112 mu m, N = 119) were mounted in microvascular myographs for isometric tension recordings. The arterioles were contracted with the thromboxane analogue, U46619, and concentration-response curves were constructed for bradykinin and a novel opener of SKCa and IKCa channels, NS309. RESULTS. In U46619-contracted arterioles, bradykinin and NS309 induced concentration-dependent relaxations. In vessels without endothelium, bradykinin relaxation was abolished and NS309 relaxation was attenuated. Inhibition of NO synthase with asymmetric dimethylarginine and/or cyclooxygenase with indomethacin markedly reduced bradykinin and NS309 relaxation. NO synthase and cyclooxygenase inhibition together with oxyhemoglobin abolished bradykinin relaxation and attenuated NS309 relaxation. Blocking of SKCa and IKCa channels with apamin plus charybdotoxin or blocking of SKCa channels alone in the absence and the presence of indomethacin markedly reduced bradykinin and NS309 relaxation, whereas blocking of IKCa channels had no significant effect. In vessels without endothelium, blocking of SKCa channels alone had no effect on sodium nitroprusside-induced relaxation. CONCLUSIONS. In porcine retinal arterioles, NO and prostaglandins mediate endothelium-dependent relaxation to bradykinin and NS309. Moreover, these findings suggest that SKCa channels contribute to NO-mediated relaxation induced by bradykinin and NS309 and, hence, may play an important role in retinal arterial endothelial function. (Invest Ophthalmol Vis Sci. 2009; 50: 3819-3825) DOI: 10.1167/iovs.08-3168