The cholesterol-lowering effects of statins are mediated by HMG-CoA reductase inhibition, which can also reduce ERK activation by preventing the post-translational modification of Ras and Rho GTPases [Casey & Seabra 1996]. We have previously shown that inhibition of ERK enhances beta-adrenoceptor (-AR)-mediated vasodilatation [Uhiara et al. 2009] and so we have investigated whether statins also enhance -AR-mediated relaxation. Cumulative concentration-relaxation curves to salbutamol (10 nM - 30 M) in the presence or absence of statins were assessed in porcine coronary artery segments contracted with U46619 [Uhiara et al. 2009]. Effects of the drugs were assessed using either unpaired Student's t-test or one-way ANOVA followed by a Tukey post-hoc test, with data from at least three separate animals of either sex. Maximum relaxation responses to salbutamol were inhibited by pre-incubation with 5 M simvastatin (88 18% in controls compared to 26 12% with simvastatin; p<0.05) but not pravastatin (10 M). Mevalonolactone (250 M) had no effect on the inhibition observed with simvastatin. This sensitivity to simvastatin, but not pravastatin, could be explained by differences in lipophilicity. The lack of effect of mevalonolactone on simvastatin inhibitions suggests that the effect of simvastatin is independent of HMG-CoA reductase. A potential alternative explanation for the action of simvastatin might involve Ca²⁺-activated K⁺ channels, which have previously been reported to mediate its effects in arterial smooth muscle cells (Seto et al. 2007). Casey, P.J. & Seabra, M.C. 1996. J Biol Chem 271, 5289–5292. Seto, S.W., Au, A.L.S., Lam, T.Y., Chim, S.S.C., Lee, S.M.Y., Wan, S., Tjiu, D.C.S., Shigemura, N., Yim, A.P.C., Chan, S.W., Tsui S.K.W., Leung, G.P.H. & Kwan, Y.W. 2007. Br J Pharmacol 151, 987–997. Uhiara, C.O., Alexander, S.P.H. & Roberts, R.E. 2009. Br J Pharmacol 158, 1713-1.