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Myoendothelial coupling through Cx40 contributes to EDH‐induced vasodilation in murine renal arteries: evidence from experiments and modelling


Acta Physiologica

Published online on


Regulation of renal vascular resistance plays a major role in controlling arterial blood pressure. The endothelium participates in this regulation as endothelial derived hyperpolarization plays a significant role in smaller renal arteries and arterioles, but the exact mechanisms are still unknown. Aim To investigate the role of vascular gap junctions and potassium channels in the renal endothelial derived hyperpolarization. Methods In interlobar arteries from wild‐type and connexin40 knockout mice, we assessed the role of calcium‐activated small (SK) and intermediate (IK) conductance potassium channels. The role of inward rectifier potassium channels (Kir) and Na+/K+‐ATPases was evaluated as was the contribution from gap junctions. Mathematical models estimating diffusion of ions and electrical coupling in myoendothelial gap junctions were used to interpret the results. Results Lack of connexin40 significantly reduces renal endothelial hyperpolarization. Inhibition of SK and IK channels significantly attenuated renal EDH to a similar degree in wild‐type and knockout mice. Inhibition of Kir and Na+/K+‐ATPases affected the response in wild‐type and knockout mice but at different levels of stimulation. The model confirms that activation of endothelial SK and IK channels generates a hyperpolarizing current that enters the vascular smooth muscle cells. Also, extracellular potassium increases sufficiently to activate Kir and Na+/K+‐ATPases. Conclusion Renal endothelial hyperpolarization is mainly initiated by activation of IK and SK channels. The model shows that hyperpolarization can spread through myoendothelial gap junctions but enough potassium is released to activate Kir and Na+/K+‐ATPases. Reduced coupling seems to shift the signalling pathway towards release of potassium. However, an alternative pathway also exists and needs to be investigated.