Chronic sodium hydrosulfide treatment decreases medial thickening of intramyocardial coronary arterioles, interstitial fibrosis, and ROS production in spontaneously hypertensive rats
Chronic sodium hydrosulfide treatment decreases medial thickening of intramyocardial coronary arterioles, interstitial fibrosis, and ROS production in spontaneously hypertensive rats
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慢性硫氢化钠治疗可减少自发性高血压大鼠心肌内冠状动脉内侧增厚、间质纤维化和 ROS 产生
DOI：
10.1152/ajpheart.00088.2007
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发表时间：
2007-10-01
影响因子：
4.8
通讯作者：
Zhu, Yi-Chun
中科院分区：
文献类型：
--
作者：
Shi, Ying-Xian;Chen, Ying;Zhu, Yi-Chun
硫化氢（H2S）是一种调节心血管功能的气体递质。本研究的目的是检查的假设，慢性治疗与硫氢化钠（NaHS，H2S供体）是能够防止自发性高血压大鼠（SHR）的左心室重构。4周龄SHR接受NaHS（10、30和90 μ mol/kg/day）、NaHS（30 μ mol/kg/day）和格列本脲（5 mg.kg mol/kg/day）联合治疗、格列本脲单药治疗（5 mg/kg/day）、肼屈嗪单药治疗（10 mg/kg/day）和安慰剂治疗3个月。mol.kg在治疗期结束时，变量，如心脏的几何形状和功能，心肌内小动脉直径范围从25到100 μ m，血管周围和间质胶原蛋白含量，活性氧（ROS），巯基，共轭二烯，和DNA碱基修饰进行了检查。本研究的新发现是，长期NaHS治疗可预防心肌内小动脉肥大和心室纤维化，并降低心肌活性氧和共轭二烯水平。与格列本脲联合给药的心脏保护作用减弱，表明ATP敏感性钾通道在介导NaHS的作用中发挥作用。肼苯哒嗪引起的血压降低与NaHS治疗相比，但是，它对重塑过程或ROS和共轭二烯水平没有影响。此外，NaHS治疗引起心肌巯基水平的增加，而DNA碱基修饰不改变NaHS治疗。结论：NaHS具有上级心脏保护作用，值得进一步研究，以开发治疗高血压心脏重构的新方法。
Hydrogen sulfide ( H2S) is a gasotransmitter that regulates cardiovascular functions. The present study aimed to examine the hypothesis that chronic treatment with sodium hydrosulfide (NaHS, an H2S donor) is able to prevent left-ventricular remodeling in spontaneously hypertensive rats (SHR). Four-week-old SHR were treated with NaHS (10, 30, and 90 mu mol.kg(-1).day(-1)), a combination of NaHS (30 mu mol.kg(-1).day(-1)) and glibenclamide (5 mg.kg(-1).day(-1)), glibenclamide alone (5 mg.kg(-1).day(-1)), hydralazine alone ( 10 mg.kg(-1).day(-1)), and placebo for 3 mo. At the end of the treatment period, variables such as cardiac geometry and function, intramyocardial arterioles ranging in diameter from 25 to 100 mu m, perivascular and interstitial collagen content, reactive oxygen species (ROS), thiol groups, conjugated dienes, and DNA base modification were examined. The novel finding of the present study is that chronic NaHS treatment prevented the hypertrophy of intramyocardial arterioles and ventricular fibrosis, as well as decreased myocardial ROS and conjugated diene levels. The cardioprotective effects were blunted by coadministration of glibenclamide, suggesting a role of ATP-sensitive potassium channels in mediating the action of NaHS. Hydralazine caused a comparable reduction of blood pressure compared with NaHS treatment; however, it exerted no effect on the remodeling process or on ROS and conjugated diene levels. Moreover, NaHS treatment caused an increase in myocardial thiol group levels, whereas DNA base modification was not altered by NaHS treatment. In conclusion, the superior cardioprotective effects of NaHS treatment are worthy to be further explored to develop novel therapeutic approaches for the treatment of cardiac remodeling in hypertension.