Abstract：
Cardiovascular functions in diabetes greatly depend on constitutive NOS (cNOS) activity. A comparative study of the effects of a steroid hormone ecdysterone and enalapril, an ACE inhibitor widely used to treat cardiac disorders on cNOS, inducible NOS (iNOS), xanthine oxidoreductase (XOR) activity, RNS, ROS, and lipid peroxidation in heart tissue in experimental diabetes was conducted. The rat model of diabetes was established by streptozotocin injection. NOS activity, NO2-, NO3-, uric acid, nitrosothiols, hydroperoxide, superoxide, and diene conjugate formation were studied spectrophotomerically. In diabetes, cNOS downregulation correlated with a dramatic fall of NO2- production and ~4.5-fold elevation of nitrosothiols, which agreed with a steep rise of iNOS activity, while NO3- remained close to control. Dramatic activation of XOR was observed, which correlated with the elevation of both superoxide production and nitrate reductase activity and resulted in strong lipid peroxidation. Ecdysterone and enalapril differently affected RNS metabolism. Ecdysterone moderately restored cNOS but strongly suppressed iNOS, which resulted in the reduction of NO3-, but full restoration of NO2- production. Enalapril better restored cNOS but less effectively suppressed iNOS, which promoted NO3- formation. Both drugs similarly inhibited XOR, which equally alleviated oxidative stress and lipid peroxidation. The synergistic action of iNOS and XOR was a plausible explanation for strong lipid peroxidation, abolished by the inhibition of iNOS and XOR by ecdysterone or enalapril. Complementary effects of ecdysterone and enalapril on cNOS, iNOS, and RNS are a promising basis for their combined use in the treatment of cardiovascular disorders caused by cNOS dysfunction in diabetes.
摘要：
糖尿病的心血管功能在很大程度上取决于组成型NOS（cNOS）活性。类固醇激素蜕皮甾酮和依那普利的作用的比较研究，一种广泛用于治疗cNOS心脏疾病的ACE抑制剂，诱导型NOS（iNOS），黄嘌呤氧化还原酶（XOR）活性，RNS,ROS,并进行了实验性糖尿病心脏组织的脂质过氧化。采用链脲佐菌素注射液建立糖尿病大鼠模型。NOS活性,NO2-,NO3-,尿酸,亚硝基硫醇，氢过氧化物,超氧化物,和二烯共轭物的形成进行了分光光度法研究。在糖尿病中，cNOS下调与NO2-产生的急剧下降和亚硝基硫醇的〜4.5倍升高相关，这与iNOS活性的急剧上升一致，而NO3-仍然接近控制。观察到XOR的显著激活，这与超氧化物产生和硝酸还原酶活性的升高有关，并导致强烈的脂质过氧化。蜕皮甾酮和依那普利对RNS代谢的影响不同。蜕皮甾酮适度恢复cNOS，但强烈抑制iNOS，这导致了NO3-的减少，而是完全恢复NO2生产。依那普利能更好地恢复cNOS，但不能有效地抑制iNOS，这促进了NO3-的形成。两种药物同样抑制XOR，这同样减轻了氧化应激和脂质过氧化。iNOS和XOR的协同作用是强脂质过氧化的合理解释，通过蜕皮甾酮或依那普利抑制iNOS和XOR而消除。蜕皮甾酮和依那普利对cNOS的补充作用，iNOS,和RNS是它们联合用于治疗糖尿病中由cNOS功能障碍引起的心血管疾病的有希望的基础。
