Activation of endothelial Ca2+‐activated potassium channels can improve endothelial function in basilar arteries from diabetic rats

Abstract

Endothelium-dependent relaxation of isolated rat basilar artery to acetylcholine (ACh) can be fully accounted for by the release of endothelium-derived NO. In addition, activation of endothelial Ca2+-activated potassium channels (KCa) plays a key role in modulating ACh-stimulated production of endothelium-derived nitric oxide (NO) in this artery. Thus, we have investigated whether activation of endothelial small (SKCa) and intermediate (IKCa) KCa by 1-ethyl-2-benzimidazolinone (1-EBIO) can improve endothelial function in basilar arteries from diabetic rats. Relaxations to ACh (0.01–30 μM) were significantly depressed in isolated basilar arteries from Streptozotocin-treated (STZ) diabetic rats compared to vessels from control animals. In contrast, relaxation of basilar arteries evoked by 1-EBIO (1–300 μM), was not significantly different in arteries from STZ and control rats. Application of low concentrations of 1-EBIO (1–5 μM) significantly enhanced ACh-evoked relaxations in basilar arteries from STZ-treated rats. Pre-incubation with L-NAME abolished relaxations to ACh both in the presence and absence of 1-EBIO indicating that the enhancement of ACh-evoked responses was due to increased production of NO. Quantitative real-time PCR analysis demonstrated that mRNA levels for both SKCa and IKCa were not significantly different in basilar arteries from control and STZ-treated rats. It is concluded that activation of KCa may significantly improve endothelial function in basilar arteries from STZ-treated diabetic rats. Supported by CIHR.