Impaired NO-mediated vasodilation with increased superoxide but robust EDHF function in right ventricular arterial microvessels of pulmonary hypertensive rats
Impaired NO-mediated vasodilation with increased superoxide but robust EDHF function in right ventricular arterial microvessels of pulmonary hypertensive rats
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DOI：
10.1152/ajpheart.00548.2006
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发表时间：
2007-06-01
影响因子：
4.8
通讯作者：
Kajiya, Fumihiko
中科院分区：
文献类型：
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作者：
Kajiya, Masahito;Hirota, Masanori;Kajiya, Fumihiko
肺动脉高压 (PH) 会导致右心室 (RV) 肥大，并且根据压力超负荷的程度。最终发生心力衰竭。我们测试了以下假设：随着超氧化物水平的增加，PH-RV 中的机械应力会损害不同大小的 RV 冠状微血管的血管反应性。五周大的雄性 Sprague-Dawley 大鼠注射野百合碱 (n = 126) 以诱导 PH 或注射生理盐水作为对照 (n = 114)。 3周后。使用活体视频显微镜观察右室中的冠状动脉（直径= 30-100μm）和小动脉（直径= 100-200μm）。我们评估了单独的乙酰胆碱诱导的血管舒张，在 N-omega-硝基-L-精氨酸甲酯 (L-NAME) 存在下，在四乙铵 (TEA) 或过氧化氢酶（有或没有 L-NAME）存在下，以及在 SOD 存在下。 L-NAME和TEA对血管舒张的抑制程度分别用作内皮一氧化氮(NO)和内皮源性超极化因子(EDHF)贡献的指标。在 PH 大鼠中。乙酰胆碱诱导的血管舒张在小动脉和小动脉中均显着减弱。尤其是在小动脉中。这种血管舒张的减少主要归因于NO介导的血管反应性的减少。而 EDHF 介导的血管舒张作用相对较强。两组中过氧化氢酶对小动脉血管舒张的抑制作用与 TEA 相似。通过光泽精化学发光测量，PH 状态下 RV 组织中的超氧化物显着升高。 SOD 显着改善 PH 中乙酰胆碱诱导的血管舒张损伤。如果发生 NO 功能障碍且超氧化物水平升高，强大的 EDHF 功能将在维持冠状动脉微血管稳态方面发挥保护作用。
Pulmonary hypertension (PH) causes right ventricular (RV) hypertrophy and, according to the extent of pressure overload. eventual heart failure. We tested the hypothesis that the mechanical stress in PH-RV impairs the vasoreactivity of the RV coronary microvessels of different sizes with increased Superoxide levels. Five-week-old male Sprague-Dawley rats were injected with monocrotaline (n = 126) to induce PH or with saline as controls (n = 114). After 3 wk. coronary arterioles (diameter = 30-100 mu m) and small arteries (diameter =100-200 mu m) in the RV were visualized using intravital videomicroscopy. We evaluated ACh-induced vasodilation alone, in the presence of N-omega-nitro-L-arginine methyl ester (L-NAME), in the presence of tetraethylammonium (TEA) or catalase with or without L-NAME, and in the presence of SOD. The degree of suppression in vasodilation by L-NAME and TEA was used as indexes of the Contributions of endothelial nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF), respectively. In PH rats. ACh-induced vasodilation was significantly attenuated in both arterioles and small aretries. especially in arterioles. This decreased vasodilation was largely attributable to reduced NO-mediated vasoreactivity. whereas the EDHF-mediated vasodilation was relatively robust. The Suppressive effect on arteriolar vasodilation by catalase was similar to TEA in both groups. Superoxide, as measured by Lucigenin chemiluminescence, was significantly elevated in the RV tissues in PH. SOD significantly ameliorated the impairment of ACh-induced vasodilation in PH. Robust EDHF function will play a protective role in preserving coronary microvascular homeostasis in the event of NO dysfunction with increased superoxide levels.