Abstract
Purpose: :
Endothelial dysfunction leads to changed release of vasodilating agents from the endothelium, which may be involved in the pathogenesis of retinal vascular diseases. In this study, we investigated the role of nitric oxide (NO) synthase, cyclooxygenase, and a NO scavenger for vasodilation induced by bradykinin and NS309, an opener of calcium activated potassium channels with small (SKCa) and intermediate (IKCa) conductance in porcine retinal arterioles. In addition, we investigated the role of SKCa and IKCa channels in the bradykinin- and NS309-evoked dilation by NO-release.
Methods: :
Retinal arterioles (diameter ~112 µm, N = 122) were mounted in wire myographs for isometric tension recordings. The arterioles were pre-contracted with the thromboxane analogue, U46619, and dose-response curves for bradykinin and NS309 were performed in the presence of inhibitors of the above mentioned enzymes and channels.
Results: :
Bradykinin and NS309 induced concentration-dependent vasodilation in the pre-contracted arterioles. Bradykin-induced vasodilation was significantly higher in intact vessels than in vessels without endothelium (P < 0.0001, n = 10). Inhibition of NO synthase and/or cyclooxygenase reduced bradykinin- and NS309-induced vasodilation (P < 0.0001, n = 10 and P < 0.05, n = 12), where NO synthase inhibition had the most pronounced effect (P < 0.0001, n = 9). NO synthase and cyclooxygenase inhibition together with a NO scavenger abolished the bradykinin-evoked vasodilation (P < 0.0001, n = 7). This treatment only attenuated the NS309-evoked vasodilation (P < 0.01, n = 9), indicating no involvement of an EDHF type relaxation. Inhibition of SKCa and IKCa channels in the presence of a cyclooxygenase inhibitor, markedly reduced NO-mediated bradykinin- and NS309-induced vasodilation (P < 0.0001, n = 8 and P < 0.0001, n = 11), where inhibition of SKCa channels alone (P < 0.01, n = 7) blunted the response most.
Conclusions: :
Mainly NO, but also prostacyclin, were found to be involved in bradykinin and NS309-evoked vasodilation in porcine retinal arterioles. SKCa and IKCa channels were involved in the bradykinin- and NS309-induced release of NO, whereas EDHF was not involved in endothelium-dependent vasodilation. These data suggest that modulation of SKCa and IKCa channels can lead to an increased release of NO from the endothelium and increase retinal blood flow. This may be involved in the development of retinal diseases, where hyperperfusion is part of the pathogenesis.
Keywords: nitric oxide • retina • blood supply