Characterization of a novel, water-soluble hydrogen sulfide - Releasing molecule (GYY4137): New insights into the biology of hydrogen sulfide
Characterization of a novel, water-soluble hydrogen sulfide - Releasing molecule (GYY4137): New insights into the biology of hydrogen sulfide
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DOI：
10.1161/circulationaha.107.753467
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发表时间：
2008-05-06
期刊：
影响因子：
37.8
通讯作者：
Moore, Philip K.
中科院分区：
文献类型：
--
作者：
Li, Ling;Whiteman, Matthew;Moore, Philip K.
背景 - 近年来，硫化氢 (H2S) 的潜在生物学意义引起了越来越多的关注。本研究的目的是表征一种新型水溶性缓释 H2S 化合物 [吗啉- 4-鎓 4 甲氧基苯基（吗啉代）二硫代膦 (GYY4137)] 并评估其作为研究该气体心血管生物学工具的用途。方法和结果 - 在体外和麻醉大鼠中评估药物对大鼠主动脉环和灌注大鼠肾的急性血管舒张作用体内。通过尾套体积描记法测定 GYY4137 对正常血压和自发性高血压大鼠血压的慢性影响。 GYY4137 在体外水溶液中以及在体内麻醉大鼠静脉内或腹膜内给药后均缓慢释放 H2S。 GYY4137 引起大鼠主动脉环缓慢舒张，并通过打开血管平滑肌 K-ATP 通道扩张灌注的大鼠肾脉管系统。 GYY4137在体外不影响大鼠心率或收缩力。 GYY4137 表现出抗高血压活性，其证据是能够减少麻醉大鼠中 N-G-硝基-L-精氨酸甲酯诱发的高血压，以及在自发性高血压大鼠中长期（14 天）给药后。结论 - 这些结果表明 GYY4137 是一种缓慢释放 H2S 化合物，具有血管扩张和抗高血压活性。 GYY4137 可能在研究 H2S 的多种生物效应中发挥作用。 GYY4137也可能被证明对心血管疾病具有治疗价值。
Background - The potential biological significance of hydrogen sulfide ( H2S) has attracted growing interest in recent years. The aim of this study was to characterize a novel, water- soluble, slow- releasing H2S compound [ morpholin- 4- ium 4 methoxyphenyl( morpholino) phosphinodithioate ( GYY4137)] and evaluate its use as a tool to investigate the cardiovascular biology of this gas.Methods and Results - The acute vasorelaxant effect of drugs was assessed in rat aortic rings and perfused rat kidney in vitro and in the anesthetized rat in vivo. The chronic effect of GYY4137 on blood pressure in normotensive and spontaneously hypertensive rats was determined by tail- cuff plethysmography. GYY4137 released H2S slowly both in aqueous solution in vitro and after intravenous or intraperitoneal administration in anesthetized rats in vivo. GYY4137 caused a slow relaxation of rat aortic rings and dilated the perfused rat renal vasculature by opening vascular smooth muscle K-ATP channels. GYY4137 did not affect rat heart rate or force of contraction in vitro. GYY4137 exhibited antihypertensive activity as evidenced by ability to reduce N-G- nitro- L- arginine methyl ester - evoked hypertension in the anesthetized rat and after chronic ( 14- day) administration in spontaneously hypertensive rats.Conclusions - These results identify GYY4137 as a slow- releasing H2S compound with vasodilator and antihypertensive activity. GYY4137 is likely to prove useful in the study of the many and varied biological effects of H2S. GYY4137 may also prove of therapeutic value in cardiovascular disease.