Deficiency of iNOS does not attenuate severe congestive heart failure in mice
Deficiency of iNOS does not attenuate severe congestive heart failure in mice
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DOI：
10.1152/ajpheart.00245.2004
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发表时间：
2005-01-01
影响因子：
4.8
通讯作者：
Lefer, DJ
中科院分区：
文献类型：
--
作者：
Jones, SP;Greer, JJM;Lefer, DJ
诱导型一氧化氮合酶 (iNOS) 与充血性心力衰竭 (CHF) 的病理生理学有关。鉴于支持这一概念的大量证据，我们假设 iNOS 缺乏 (iNOS(-/-)) 会减轻小鼠 CHF 的严重程度。小鼠的左冠状动脉前降支近端永久闭塞[心肌梗死(MI)]以产生CHF。使用超声心动图和超小型心室压力导管在体内评估心脏功能。对假野生型 (n = 17)、假 iNOS(-/-) (n = 8)、MI 野生型 (n = 56) 和 MI iNOS(-/-) (n = 48) 小鼠进行 MI（或假 MI）并随访 1 个月。与野生型相比，iNOS 缺乏不会改变 CHF 期间的生存率（35% 与 32%，P = 不显着）。此外，野生型（9.6 +/- 2.0% 和 441 +/- 20 mul.min(-1).g(-1)）和 iNOS（-/-）（9.8 +/- 1.3% 和 471 +/- 26 mul.min(-1).g(-1)）小鼠之间的缩短分数和心输出量没有显着差异。野生型和iNOS(-/-)小鼠的心脏肥大和肺水肿的程度也相似。所有指标均未显示出 iNOS(-/-) 与遭受 MI 的野生型小鼠之间存在任何显着差异。这些发现表明，iNOS 缺乏不会显着影响 MI 后小鼠的严重 CHF。
Inducible nitric oxide synthase (iNOS) has been implicated in the pathophysiology of congestive heart failure (CHF). Given the extensive evidence supporting this concept, we hypothesized that iNOS deficiency (iNOS(-/-)) would attenuate the severity of CHF in mice. Mice were subjected to permanent occlusion [myocardial infarction (MI)] of the proximal left anterior descending coronary artery to produce CHF. Cardiac function was assessed in vivo using echocardiography and ultraminiature ventricular pressure catheters. Sham wild-type (n = 17), sham iNOS(-/-) (n = 8), MI wild-type (n = 56), and MI iNOS(-/-) (n = 48) mice were subjected to MI (or sham MI) and followed for 1 mo. Deficiency of iNOS did not alter survival during CHF compared with wild type (35% vs. 32%, P = not significant). Furthermore, fractional shortening and cardiac output were not significantly different between wild-type (9.6 +/- 2.0% and 441 +/- 20 mul.min(-1).g(-1)) and iNOS(-/-) (9.8 +/- 1.3% and 471 +/- 26 mul.min(-1).g(-1)) mice. The extent of cardiac hypertrophy and pulmonary edema was also similar between wild-type and iNOS(-/-) mice. None of the indexes demonstrated any significant differences between iNOS(-/-) and wild-type mice subjected to MI. These findings indicate that deficiency of iNOS does not significantly affect severe CHF in mice after MI.