The Kv7 channel activator, retigabine, induces vasorelaxation via an endothelial-independent pathway in male mouse aorta.

Abstract

[Purpose]Previous studies have indicated that Kv7 channels have an important role in the regulation of blood vessel reactivity, including in the coronary, renal, and cerebral arteries. The present studies examined whether Kv7 channels regulated vascular reactivity in the mouse aorta and investigated the mechanisms involved in the reactivity.[Methods]Wild-type (WT) male C57BL/6 mice, between 10 and 15 weeks old, were used in this study. The vascular function of the aorta in WT male mice was assessed by using a pin myography system (Model 620; DMT, Denmark).[Results]Vasorelaxation by an endothelial-dependent vasodilator, acetylcholine (ACh, 1 nM – 10 μM) and an endothelial-independent vasodilator, sodium nitroprusside (SNP, 1 nM – 10 μM) was induced in the aorta in a dose-dependent manner. Pre-incubation with the nitric oxide synthase inhibitor, L-NAME (100 μM, 20 min), completely abolished ACh-induced vasorelaxation, but did not block retigabine-induced vasorelaxation, which suggested that retigabine caused vasorelaxation in the aorta via smooth muscle activation rather than via endothelial cells. Pre-application of the Kv7 channel blocker, linopirdine (10 μM), resulted in a greater contractile response compared with that induced by vehicle in the aorta. In addition, pre-incubation with linopirdine (10 μM, 20 min) reduced retigabine-induced vasorelaxation (1–50 μM).[Conclusion]This study has provided evidence that Kv7 channels may play a role in the regulation of aortic blood flow via smooth muscle activation.