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A group of nitrate derivatives of naturally occurring sauropunol A and B were designed and synthesized. Nitric oxide (NO) releasing capacity and vasodilatory capacity studies were performed to explore the structure-activity relationship of resulted nitrates. Biological evaluation of these compounds revealed that most of the synthesized mononitrate derivatives demonstrated superior releasing capacity than isosorbide mononitrate (ISMN), and <b>2MNS-6</b> even demonstrated stronger NO releasing capacity than isosorbide dinitrate (ISDN). Two dinitrates, <b>DNS-1</b> and <b>DNS-2</b>, showed higher NO releasing capacity than ISDN. Evaluation of inhibitory activities to the contractions in mesenteric artery rings revealed that <b>2MNS-8</b> and <b>DNS-2</b> showed stronger vasorelaxation activities than ISDN. High level of NO and soluble guanylyl cyclase (sGC) may be essential for the potent vasodilatory effect of <b>DNS-2</b>. The vasodilatory effects of <b>DNS-2</b> may result from cellular signal transduction of NO-sGC-cGMP. <b>DNS-2</b> was found to be the most potent sauropunol-derived nitrate vasodilatory agent for further pharmaceutical investigation against cardiovascular diseases.