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• W2066733750 abstract "Hydrogen sulfide (H2S) has only relatively recently been recognised as an important endogenous mediator of vascular relaxation and a range of other regulatory processes. Despite the potential of H2S as a treatment for a range of diseases, it has not yet been incorporated in clinical practice, possibly because of concerns over control of dosage and method of delivery. Metal organic frameworks (MOFs) have potential to provide targeted, flexible applications in gasotransmitter delivery. Here, we describe release and bioactive properties of three designs of MOF loaded with H2S. MOFs derived from 2,5-dihydroxyterephthalic acid and nickel (Ni2(dhtp)), magnesium (Mg2(dhtp)) or magnesium doped with nickel (10 wt%; Ni2/Mg2(dhtp)) were prepared and pressed into 20 mg discs containing 10 wt% Teflon. The discs were dehydrated under vacuum at high temperature, cooled and exposed to an atmosphere of H2S. 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 37 °C [1]. Pig hearts were obtained from an abattoir and in vitro coronary artery endothelial cell (EC) function (relaxation to bradykinin; BK, 1 nM–10 μM) was measured in arteries by myography. Segments with or without an intact endothelium (EC removed by gentle abrasion with forceps) were then exposed for 30 min to H2S-loaded MOFs Ni2(dhtp), Mg2(dhtp) or Ni2/Mg2(dhtp). In separate experiments, release of H2S from the different MOFs bathed in phosphate-buffered saline at 37 °C was individually measured in an enclosed chamber using an ISO-H2S-2 probe (n = 3 per MOF). Relaxation data are presented as mean ± SEM; statistical analysis was by t-test or 2-way ANOVA with post hoc analysis, as appropriate. Pig coronary arteries constricted with 0.1 μM U46619 showed significantly greater relaxation in the presence of H2S-loaded Ni2(dhtp) (+EC: 83.7 ± 4.9%, n = 5; -EC: 86.2 ± 0.9%, n = 3, both p < 0.0001 vs. Ni2/Mg2(dhtp)), and Mg2(dhtp) (+EC: 89.7 ± 2.0%, n = 5; -EC: 86.7 ± 2.1%, n = 5, both p < 0.0001 vs Ni2/Mg2(dhtp)), compared to Ni2/Mg2(dhtp) MOFs (+EC: 5.3 ± 6.9%, n = 6; -EC: 15.7 ± 4.4%, n = 4), irrespective of whether or not the endothelium was intact. Unloaded MOFs induced no vascular reactivity (data not shown). The peak release of H2S from Ni2(dhtp) and Mg2(dhtp) MOFs was approximately 7 times that from Ni2/Mg2(dhtp) MOFs. The data indicate that capacity for storage and release of H2S is much greater in MOFs which use only Ni2+ or Mg2+ as the core metal ion rather than Mg2+ doped with Ni2+, and that corresponding relaxation responses in intact arteries by H2S are not mediated by endothelium-dependent signalling pathways. These results confirm that delivery and bioactivity potential for H2S from MOFs can be controlled by manipulating the MOF structure. This work was funded by the British Heart Foundation." @default.
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• W2066733750 date "2013-09-01" @default.
• W2066733750 modified "2023-09-26" @default.
• W2066733750 title "OP32 Vascular reactivity in response to release of hydrogen sulfide from metal organic frameworks" @default.
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• W2066733750 doi "https://doi.org/10.1016/j.niox.2013.06.062" @default.
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