KCNQ genes encode the Kv7 class of voltage-gated potassium channels, which play important roles in the heart, inner ear and brain. It was recently suggested that Kv7 channels may conduct the background K+ conductance in pulmonary artery smooth muscle cells (PASMCs) (Joshi et al., 2008). Fenamate drugs have been found to activate Kv7 channels (Gribkoff et al., 2008) and, as such, they may help us to understand the function of Kv7 channels within PASMCs. The effects of mefenamic acid (MFA) and meclofenamic acid (MCFA) were investigated on the contractile properties of pulmonary arteries (PA) from male Sprague-Dawley rats using wire myography. PASMCs were isolated and used for electrophysiological recording with the whole-cell, patch-clamp technique. Both MFA and MCFA dilated phenylephrine (1μM) pre-constricted PA with EC50 values of 28 and 14 μM, respectively. The dilation was reduced when vessels were pre-constricted with 50mM K+ and abolished in low Cl- (8mM) solution. Both drugs hyperpolarised the cell membrane, MFA by -8 ± 3 mV (n=7) at 50 μM and MCFA by 14 ± 2 mV (n=9) at 25 μM, a maximally effective concentration. Unexpectedly, MCFA (25 μM) failed to enhance the non-inactivating, background K+ current measured at 0 mV, instead reducing it from 49 ± 5 pA to 31 ± 3 pA (n=3; p<0.05). Setting the K+ equilibrium potential to 0 mV, by raising the extracellular K+ concentration, revealed a non-inactivating current at potentials negative to -50mV, which disappeared when intracellular K+ was substituted with Cs+. In most cells this current was clearly inhibited by 50μM MCFA, suggesting that MCFA blocks a K+ channel that is open at the resting membrane potential. Fenamates hyperpolarise PASMC and dilate PA, but not as a consequence of K+ channel activation. Abolition of the dilator effect in low Cl- solution suggests that blockade of Cl-channels is a more likely mechanism.