Pressure overload-induced LV hypertrophy and dysfunction in mice are exacerbated by congenital NOS3 deficiency
Pressure overload-induced LV hypertrophy and dysfunction in mice are exacerbated by congenital NOS3 deficiency
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DOI：
10.1152/ajpheart.00940.2003
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发表时间：
2004-03-01
影响因子：
4.8
通讯作者：
Scherrer-Crosbie, M
中科院分区：
文献类型：
--
作者：
Ichinose, F;Bloch, KD;Scherrer-Crosbie, M
为了研究内皮型一氧化氮合酶（NOS3）在慢性压力过载引起的左室重构中的作用，我们比较了野生型（WT）和NOS3缺陷型（-/-）小鼠主动脉横缩（TAC）对左室结构和功能的影响。在TAC前，两个小鼠品系的左室壁厚度、质量和分数缩短相似。TAC后28天，WT和NOS3（-/-）小鼠左室壁厚度和质量均增加，缩短率降低。虽然两种小鼠在TAC后28天的压力梯度相似，但NOS3小鼠的左室质量和后壁厚度比WT小鼠大（-/-），而左室压力的分数缩短和最大发展率则更小。通过等容舒张时间常数和最大左室压衰减率测量，NOS3-/-小鼠的舒张功能受损程度大于WT小鼠。TAC后28天，NOS3小鼠心肌细胞肥大和左室纤维化程度（-/-）高于WT小鼠。TAC后28天NOS3（-/-）小鼠的死亡率高于WT小鼠。长期给药肼能使NOS3（-/-）小鼠血压正常化，并阻止左室扩张，但不能预防TAC后NOS3缺乏引起的左室肥大、功能障碍和纤维化。这些结果表明，在慢性压力过载小鼠模型中，NOS3的缺失增加了左室功能障碍和重塑。
To investigate the role of endothelial nitric oxide synthase (NOS3) in left ventricular (LV) remodeling induced by chronic pressure overload, the impact of transverse aortic constriction (TAC) on LV structure and function was compared in wild-type (WT) and NOS3-deficient (NOS3(-/-)) mice. Before TAC, LV wall thickness, mass, and fractional shortening were similar in the two mouse strains. Twenty-eight days after TAC, both WT and NOS3(-/-) mice had increased LV wall thickness and mass as well as decreased fractional shortening. Although the pressure gradient across the TAC was similar in both strains of mice 28 days after TAC, LV mass and posterior wall thickness were greater in NOS3(-/-) than in WT mice, whereas fractional shortening and the maximum rate of developed LV pressure were less. Diastolic function, as measured by the time constant of isovolumic relaxation and the maximum rate of LV pressure decay, was impaired to a greater extent in NOS3-/- than in WT mice. The degree of myocyte hypertrophy and LV fibrosis was greater in NOS3(-/-) than in WT mice at 28 days after TAC. Mortality was greater in NOS3(-/-) than in WT mice 28 days after TAC. Long-term administration of hydralazine normalized the blood pressure and prevented the LV dilation in NOS3(-/-) mice but did not prevent the LV hypertrophy, dysfunction, and fibrosis associated with NOS3 deficiency after TAC. These results suggest that the absence of NOS3 augments LV dysfunction and remodeling in a murine model of chronic pressure overload.