Hataishi Ryuji, Rodrigues Ana Clara, Morgan John G, Ichinose Fumito, Derumeaux Geneviève, Bloch Kenneth D, Picard Michael H, Scherrer-Crosbie Marielle
Department of Anaesthesia and Critical Care, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA.
Exp Physiol. 2006 May;91(3):633-9. doi: 10.1113/expphysiol.2005.033068. Epub 2006 Mar 9.
Nitric oxide synthase 2 (NOS2) has been reported to increase in hypertrophied cardiomyocytes; however, whether NOS2 plays a role in the development of hypertrophy is unknown. To investigate the relationship of NOS2 with left ventricular (LV) remodelling and hypertrophy following prolonged pressure overload, we studied 18 male wild-type (WT) and 20 male NOS2-deficient (NOS2-/-) mice before and 7, 14 and 28 days after transverse aortic constriction (TAC) using echocardiography. A subgroup of eight WT and eight NOS2-/- mice were studied 42 days after TAC. Haemodynamic measurements were obtained before killing. Left ventricular size and function were similar for both genotypes at baseline. After TAC for 28 days, both groups developed LV hypertrophy, with echo-derived LV mass increasing from 78 +/- 2 to 147 +/- 10 mg in WT and from 86 +/- 3 to 142 +/- 10 mg in NOS2-/- mice. Twenty-eight days after TAC, LV weight and cardiomyocyte width were also similar in both genotypes. Fractional shortening (FS) decreased on day 7 from 57 +/- 1 to 48 +/- 2% in WT and from 59 +/- 1 to 49 +/- 2% in NOS2-/- mice. Although this decrease in FS was transient in WT mice, it persisted in NOS2-/- mice. Invasively measured parameters of systolic and diastolic function, however, were similar in the two genotypes both 28 and 42 days after TAC. A load-independent index of contractility, Emax, was similar in both strains 42 days after TAC. In conclusion, NOS2 does not appear to have a critical role in the development of LV hypertrophy after chronic pressure overload.
据报道，一氧化氮合酶2（NOS2）在肥大的心肌细胞中会增加；然而，NOS2是否在肥大的发展中起作用尚不清楚。为了研究NOS2与长期压力超负荷后左心室（LV）重构和肥大的关系，我们使用超声心动图对18只雄性野生型（WT）小鼠和20只雄性NOS2基因缺陷（NOS2-/-）小鼠在横向主动脉缩窄（TAC）前以及TAC后7天、14天和28天进行了研究。对8只WT小鼠和8只NOS2-/-小鼠组成的亚组在TAC后42天进行了研究。在处死前进行血流动力学测量。两种基因型在基线时左心室大小和功能相似。TAC 28天后，两组均出现左心室肥大，WT小鼠经超声心动图测量的左心室质量从78±2 mg增加到147±10 mg，NOS2-/-小鼠从86±3 mg增加到142±10 mg。TAC 28天后，两种基因型的左心室重量和心肌细胞宽度也相似。WT小鼠的缩短分数（FS）在第7天从57±1%降至48±2%，NOS2-/-小鼠从59±1%降至49±2%。虽然WT小鼠中FS的这种降低是短暂的，但在NOS2-/-小鼠中持续存在。然而，在TAC后28天和42天，两种基因型的收缩和舒张功能的有创测量参数相似。在TAC后42天，两种品系的收缩性负荷无关指标Emax相似。总之，在慢性压力超负荷后左心室肥大的发展过程中，NOS2似乎没有关键作用。
