Recently our group have shown that Kv7, voltage-gated potassium channels, encoded by the genes KCNQ1-5 are present functionally in vascular and non-vascular smooth muscle cells. In smooth muscle cells expression of Kv7.1, Kv7.4 and Kv7.5 predominates in contrast to the neuronal expression profile (Kv7.2/7.3) or the cardiac profile (Kv7.1). However, there is no information as to the role of each isoform. Recently, activators of Kv7 channels have been developed that show considerable selectivity against Kv7.1. The aim of the present study was to compare the effect of 3 activators of Kv7.2-7.5 channels, S-1, ICA27243 and retigabine in rat mesenteric and renal arteries. Segments (~3mm) of rat main renal and mesenteric artery (3rd order) were mounted on 40mm wires in a myograph (DMT, Denmark) for isometric tension recording. Vessels were contracted with 10mM Methoxamine and Kv7 activators were applied cumulatively from 10nM. Equivalent vehicle (DMSO) dilutions were applied contemporaneously. Western blot analysis was performed on rat renal and mesenteric arteries using antibodies specific for Kv7.4 and Kv7.5. Methoxamine contracted mesenteric arteries by 4.80 ± 0.422mN (n=38) that was not significantly effected by DMSO. Application of all Kv7 activators produced a concentration-dependent relaxation with a relative efficacy of S1>ICA27243> retigabine. In the renal arteries application of 10mM XE991 produced a contraction of 0.94 ± 0.36mN. Subsequent application of methoxamine produced a contraction that was not relaxed by 10mM S-1, which produced a 51.75 ± 11% relaxation in the absence of XE991 (n=5). ICA27243-induced relaxations were still recorded in the presence of XE991. Western blot analysis showed expression of Kv7.4 and Kv7.5 in both arteries. This study is the first to fully characterise the effects of various Kv7 channel activators in the rat mesenteric artery and renal artery. This is also the first study to demonstrate a role of Kv7 channels in the renal artery.