Nitric oxide (NO) donors are agents that release NO by chemical reaction, either spontaneously or under specific biophysical conditions. NO donors have been widely used in a variety of clinical situations, with mixed success 1. Alternatively, metal organic frameworks (MOFs) have potential to provide targeted, flexible applications in gasotransmitter delivery. Here, we describe bioactive properties of two designs of MOF loaded with NO. MOFs derived from 2,5-dihydroxyterephthalic acid and nickel (Ni2(dhtp)) or magnesium (Mg2(dhtp)) were prepared and pressed into 20 mg discs containing 10wt% Teflon. The discs were dehydrated under vacuum at high temperature, cooled and exposed to an atmosphere of NO. Once loaded, MOF discs were stored individually under argon until use. Unloaded discs were also prepared to act as controls. . Previous studies revealed the gas is rapidly released from the discs upon exposure to an aqueous environment at 37oC 2. Pig hearts were obtained from an abattoir and in vitro coronary artery endothelial function (relaxation to bradykinin; BK, 0.1 nM – 10 μM) was measured in arteries by myography. Segments lacking reactivity to BK following removal of the endothelium were then exposed for 10 minutes to NO-loaded MOFs Ni2(dhtp) or Mg2(dhtp). In separate experiments, human umbilical vein endothelial cells (HUVEC), passage 1 to 3, were exposed for 1, 6, 24 or 72h to medium conditioned for 1h in the presence of unloaded Ni2(dhtp) and Mg2(dhtp) MOFs to assess toxicity by MTT assay. Data are presented as mean ± SEM; statistical analysis was by t-test or 2-way ANOVA with post hoc analysis, as appropriate. Endothelium-denuded pig coronary arteries constricted with 0.1 µM U46619, a thromboxane mimetic, showed significantly greater relaxation in the presence of NO-loaded Ni2(dhtp) compared to Mg2(dhtp) MOFs (59.1±9.4%, n=5 vs 9.5±3.5%, n=3; p 0.004). Unloaded MOFs induced no vascular reactivity (data not shown). Colourimetric analysis of mitochondrial activity (MTT assay) in HUVECs showed significantly greater toxicity of Ni2(dhtp) than Mg2(dhtp) MOF-conditioned medium at all time-points except 1h (fig 1). The data indicate that capacity for storage and release of NO is much greater in MOFs which use Ni2+ as the core metal ion rather than Mg2+, but the greater performance in releasing biologically relevant amounts of NO is, in this case, offset by an increased risk of toxicity to endothelial cells. Use of the Ni2(dhtp) MOF design for delivery of gasotransmitters in pathophysiological settings should be restricted to procedures which do not involve chronic exposure of endothelium. Other more sensitive bioassays are required to fully assess the potential of Mg2(dhtp) MOFs.