Dias Fernando A L, Urboniene Dalia, Yuzhakova Milana A, Biesiadecki Brandon J, Pena James R, Goldspink Paul H, Geenen David L, Wolska Beata M
Department of Medicine, Section of Cardiology, Center for Cardiovascular Research, University of Illinois at Chicago, IL 60612, USA.
Front Biosci (Elite Ed). 2010 Jan 1;2(1):312-24. doi: 10.2741/e92.
We investigated the role of inducible NOS (iNOS) on cardiac function during the development of left ventricular hypertrophy. Hypertrophy was induced by pressure-overload via short-term (2.5 months) or long-term (6.5 months) aortic banding (AoB) in wild-type (WT) and iNOS knock out (iNOSKO) mice. Cardiac function was then assessed via echocardiography, in situ hemodynamics and papillary muscle force measurements. Quantitative RT-PCR and Western blots were used to measure expression of hypertrophic gene markers and proteins respectively. Our data demonstrate that increased afterload via AoB leads to increased expression of iNOS that is associated with cardiac dysfunction. In pressure-overload induced hypertrophy, iNOSKO delays both the expression of hypertrophic markers and contractile dysfunction without causing significant changes in the level of hypertrophy. Moreover, after long-term AoB, iNOSKO animals exhibited increased basal cardiac function and an improved response to beta-adrenergic stimulation compared to long-term AoB WT animals. In conclusion, our data demonstrate that NO production via iNOS plays an important role in modulating cardiac function after moderate AoB that mimics long-term hypertension in humans.
我们研究了诱导型一氧化氮合酶（iNOS）在左心室肥厚发展过程中对心脏功能的作用。通过对野生型（WT）和iNOS基因敲除（iNOSKO）小鼠进行短期（2.5个月）或长期（6.5个月）主动脉缩窄（AoB）来诱导压力超负荷引起的肥厚。然后通过超声心动图、原位血流动力学和乳头肌张力测量来评估心脏功能。分别使用定量逆转录聚合酶链反应（RT-PCR）和蛋白质免疫印迹法来测量肥厚基因标志物和蛋白质的表达。我们的数据表明，通过AoB增加后负荷会导致与心脏功能障碍相关的iNOS表达增加。在压力超负荷诱导的肥厚中，iNOSKO延缓了肥厚标志物的表达和收缩功能障碍，而不会导致肥厚程度的显著变化。此外，与长期AoB的WT动物相比，长期AoB后，iNOSKO动物表现出基础心脏功能增加以及对β-肾上腺素能刺激的反应改善。总之，我们的数据表明，通过iNOS产生的一氧化氮（NO）在模拟人类长期高血压的中度AoB后调节心脏功能中起重要作用。
