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Recently, periadventitial adipose tissue (PAT) was found to secrete bioactive factors playing an important role in the regulation of vascular tension. Hydrogen sulfide (H2S), a novel cardiovascular gasotransmitter, relaxes vessels through the KATP channel in a calcium-dependent and endothelial-independent manner.We first identified the endogenous H2S-generated key enzyme cystathionase (CSE) expressed in adipocytes of PAT and H2S released from PAT in rats.The CSE inhibitors DL-propargylglycine and/or beta-cyano-L-alanine largely blocked the vasorelaxing effects on aorta rings (removed adventitia), induced by PAT, the culture medium of PAT or isolated adipocytes from PAT. Phenylephrine, serotonin and angiotensin II inhibited endogenous H2S production from the aortic medium but increased its release from PAT. Endogenous H2S generated in the aorta and PAT was decreased but the level of CSE protein was increased with the aging of rats. In rats with hypertension induced by abdominal aortic banding, H2S generation and CSE protein expression were significantly increased in PAT but not aortic tissues. Transplanting PAT into periadventitia of stenotic aortas ameliorated the elevated arterial blood pressure and decreased angiotensin II level in aorta.These results suggested PAT could endogenously generate H2S, which might act as an adipocyte-derived relaxing factor and contribute to the pathogenesis of hypertension.