Drachuk K O, Dorofeyeva N A, Sagach V F
Fiziol Zh (1994). 2016;62(6):9-18. doi: 10.15407/fz62.06.009.
The objective of the study was to examine the effect of exogenous hydrogen sulde donor; sodium hydrosulfide (NaHS), on thefree radical generation, cNOS uncoupling in the myocardium, and diastolicfunction in old rats. To evaluate diastolic function of the heart, we used pressure-volume (PV) conductance catheter system (Millar Instruments, USA). It was shown that H2S levels in. the isolated mitochondria and whole heart homogenates obtained from old age rats were significantly lower comparing with adult animals. The markers of combined oxidative and nitrosative stress (the rate of 0 ₂⁰ H generation, pools of H₂0₂, diene conjugates, malondialdehyde, uric acid, the activity of iNOS, nitrate reductase, and NO pools) were increased in the old hearts in line with cNOS uncoupling. Such changes in NOS coupling resulted in the loss of diastolic relaxation (decrease of the rate of relaxation of the left ventricle (dp/dtmin) by 33%, 3-times increase of the end-diastolic pressure, 1.5-time increase of the time constant of left ventricular relaxation (Tau g) and 2-time increase of the end-diastolic stiffness). It has been found that NaHS inhibits oxidative and nitrosative stress, restores cNOS coupling and constitutive de novo synthesis of nitric oxide (NO), which promotes an improvement of the diastolic function (increase of the dp/dtmin by 20% and decrease of Tau g by 13%) . Key words: aging; cNOS uncoupling; heart; hydrogen sulfide; nitrosative stress; oxidative stress.
本研究的目的是检测外源性硫化氢供体硫氢化钠（NaHS）对老年大鼠心肌自由基生成、cNOS解偶联及舒张功能的影响。为评估心脏舒张功能，我们使用了压力-容积（PV）电导导管系统（美国Millar仪器公司）。结果显示，与成年动物相比，老年大鼠分离的线粒体和全心肌匀浆中的硫化氢水平显著降低。老年心脏中，氧化应激和亚硝化应激联合标志物（O₂⁰H生成速率、H₂O₂池、二烯共轭物、丙二醛、尿酸、诱导型一氧化氮合酶活性、硝酸还原酶及一氧化氮池）随cNOS解偶联而增加。一氧化氮合酶偶联的这种变化导致舒张期松弛丧失（左心室松弛速率（dp/dtmin）降低33%，舒张末期压力增加3倍，左心室舒张时间常数（Tau g）增加1.5倍，舒张末期硬度增加2倍）。研究发现，NaHS可抑制氧化应激和亚硝化应激，恢复cNOS偶联及一氧化氮（NO）的组成性从头合成，从而促进舒张功能改善（dp/dtmin增加20%，Tau g降低13%）。关键词：衰老；cNOS解偶联；心脏；硫化氢；亚硝化应激；氧化应激。
