Introduction and objective: 3-Hydroxy-3-methylglutaryl (HMG)-CoA reductase inhibitors, statins, provide beneficial acute effects independent of their lipid-lowering actions. One such effect is cardioprotection. However, the acute effects of statins on resistance arterial function are not completely understood. In the present study, we examined if acute simvastatin incubation modulated rat mesenteric resistance artery (MRA) function. Methods: Male Wistar rats (3-4months) were killed by cervical dislocation. Third or fourth order MRA (2-4 mm in length) were dissected out and mounted on a wire myograph. Tissues were bathed in physiological salt solution (PSS) at 370C aerated with 20% O2/ 5% CO2, normalized and equilibrated for 30 minutes. Functional integrity was assessed by 1) contraction to 120 mM KPSS and 2) relaxation to acetylcholine (ACh, 10 µM) in U46619 (1 µM) pre-contracted rings. To examine the acute effects of simvastatin, MRA were then incubated with or without Simvastatin (0.1 or 1 µM) for 1 or 2hs and concentration-response curves to U46619 (10-10 – 10-6 M), ACh (10-9 – 10-5 M) and sodium nitropusside (SNP, 10-9 – 10-4 M) constructed. To evaluate the role of NO on the effects of simvastatin (1 µM, 2hs), experiments were repeated in MRA incubated with L-NNA (10 µM) (NO synthase inhibitor). Results were analysed using one- or two-way ANOVA using Bonferroni’s post hoc test. Differences were considered statistically significant at P<0.05. Results: Incubation with 0.1 μM simvastatin for 2hs had no significant effect on either maximal response (Control: 104±5 (N=12) vs. Simvastatin 0.1 µM: 112±7 % of KPSS (N=6) or the sensitivity to U46619 (Control: 6.78±0.09 vs. Simvastatin 0.1 µM; 6.80±0.15). However 1 μM simvastatin for 2hs significantly reduced the maximal response (52±13 % of KPSS-induced contraction (N=10); P<0.05) but did not change the sensitivity to U46619 (6.70±0.04). Simvastatin had no effect on responses to ACh or SNP at any concentration (ACh; Emax, Control: 89±3 vs. Simvastatin 0.1 µM: 92±3 vs. Simvastatin 1 µM: 79±5 % of relaxation and SNP; Emax, Control: 85±4 vs. Simvastatin 0.1 µM: 88±3 vs. Sinvastatin 1 µM: 83±4 % of relaxation). Similar effects were observed after 1 h incubation. L-NNA incubation reversed the effect of 1 µM simvastatin on the U46619-induced contraction of MRA (Emax, Control + L-NNA: 107±6 vs. Sinvastatin 1 µM + L-NNA: 100±12 % of KPSS-induced contraction). Conclusion: Acute simvastatin treatment reduces the contraction of rat MRA to U46619 by a NO-dependent mechanism. This could explain the beneficial effect of acute statin on cardioprotection.