Isoproterenol-induced heart failure in the rat is associated with nitric oxide-dependent functional alterations of cardiac function
Isoproterenol-induced heart failure in the rat is associated with nitric oxide-dependent functional alterations of cardiac function
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DOI：
10.1093/eurjhf/hfn026
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发表时间：
2009-02-01
影响因子：
18.2
通讯作者：
Kyselovic, Jan
中科院分区：
文献类型：
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作者：
Krenek, Peter;Kmecova, Jana;Kyselovic, Jan
一氧化氮（NO）在心力衰竭（HF）中的作用是复杂的，仍然存在争议。我们测试的假设，即NO在离体心房和心肌细胞的作用是改变异丙肾上腺素诱导的HF。大鼠接受异丙肾上腺素（ISO，5毫克/公斤/天，腹腔注射）或车辆1周。通过左心室插管获得血流动力学参数。测定NOS抑制对离体心房和电起搏左心室肌细胞的影响。此外，一氧化氮合酶及其变构调节剂热休克蛋白90，小窝蛋白-1，小窝蛋白-3蛋白在左心室的表达进行了测量。ISO使左室重量增加33%，左室收缩和舒张功能指标dp/dt（min）和dp/dt（max）降低（均P < 0.05）。HF大鼠离体心房的自发搏动频率明显降低（P < 0.05）。NOS抑制可使HF组基础频率增加，并减弱β-肾上腺素能刺激的正性变时作用（P < 0.05）。衰竭心脏的心室肌细胞缩短受损。L-NAME降低对照组的收缩力，但不影响心肌细胞的收缩力。左心室eNOS、hsp 90、iNOS的表达增加，但nNOS和caveolins没有增加。尽管异丙肾上腺素诱导的HF中NO合成能力增加，但NO不能维持衰竭心肌细胞的收缩力。NO可能导致基础心率下降，并可能加速变时性的β-肾上腺素能刺激。
The role of nitric oxide (NO) in heart failure (HF) is complex and remains controversial. We tested the hypothesis that the role of NO in isolated atria and cardiomyocytes is altered in isoproterenol-induced HF.Rats received isoproterenol (ISO, 5 mg/kg/day, intraperitoneally) or vehicle for 1 week. Haemodynamic parameters were obtained by left ventricular catheterization. Effects of NOS inhibition on isolated atria and on electrically paced left ventricular myocytes were determined. Additionally, expressions of nitric oxide synthases and their allosteric modulators hsp90, caveolin-1, and caveolin-3 proteins in the left ventricles were measured. ISO increased left ventricular mass by 33% and decreased indices of left ventricular systolic and diastolic function dp/dt(min) and dp/dt(max) (both P < 0.05). Isolated atria from HF rats had a lower spontaneous beating rate (P < 0.05). NOS inhibition by L-NAME increased basal frequency and attenuated the positive chronotropic effect of beta-adrenergic stimulation in the HF group (P < 0.05). Ventricular myocytes from failing hearts had impaired cell shortening. L-NAME decreased contractility of control, but not failing myocytes. Left ventricular expressions of eNOS, hsp90, iNOS, but not nNOS or caveolins, were increased.Despite the increased capacity for NO synthesis in isoproterenol-induced HF, NO does not sustain contractility of failing myocytes. NO may contribute to the decreased basal heart rate and it may accelerate beta-adrenergic stimulation of chronotropy.