Vascular relaxation is mediated by a range of endogenous factors, including hydrogen sulphide (H2S) and acute hypoxia. The mechanisms by which these factors elicit vasorelaxation have not been fully elucidated. Relaxation to H2S is O2-sensitive [1], and transient receptor potential A1 knockout mice (TRPA1-/-) show an attenuated ear perfusion response to an H2S donor [2]. Therefore we investigated whether relaxation to H2S in porcine coronary arteries is mediated by TRPA1, and if H2S and hypoxia share a common mechanism of action.Pure H2S was administered in a controlled manner by metal organic frameworks (MOFs). MOFs derived from 2,5-dihydroxyterephthalic acid and magnesium (Mg2(dhtp)) were prepared and pressed into 20 mg discs containing 10% Teflon (by weight). 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. Previous studies revealed the gas is rapidly released from the discs upon exposure to an aqueous environment at 37○C [3]. Pig hearts were obtained from an abattoir and segments of coronary artery with or without an intact endothelium (± EC) were assessed ex vivo by wire myography. Pre-constriction to 0.1 µM U46619 was followed by incubation with hypoxia (gassing chambers with 95% N2/ 5% CO2) for 1h, or HC-030031 (selective TRPA1 inhibitor; 10 µM) for 30 min, or consecutive incubation with both, then exposure for 30 min to H2S-loaded MOFs. Percent relaxation data are presented as mean ± SEM, n=5-6 per group; statistical analysis was by 2-way ANOVA with post hoc analysis.Potent relaxation occurred in normoxic arteries in response to H2S (+EC: 90±2; -EC: 86±1.5; ns). Hypoxia caused vasorelaxation, significantly more so in the presence of an intact endothelium (+EC: 55±7; -EC: 22±8; p <0.05), while HC-030031 was not vasoactive. Hypoxia and inhibition of TRPA1 channels individually attenuated relaxation to H2S, but while the effect of hypoxia on H2S was unmodified by endothelial status (+EC: 54±19; -EC: 42±7; ns), HC-030031 completely ablated relaxation to H2S only in arteries with a functional endothelium (+EC: -1±13, -EC: 51±12; p <0.05). Hypoxia in addition to HC-030031 did not alter the degree of attenuation of relaxation to H2S compared to hypoxia alone (+EC: 27±14; -EC: 33±5; ns by EC status or treatment group).The data show that TRPA1 channels mediate relaxation to H2S in porcine coronary arteries, but that the role of these receptors may be principally associated with the endothelium. The data do not support a common mechanism of action for hypoxia and H2S in inducing vasorelaxation, although both appear to be mediated, in part, by TRPA1 channel activity.