Objective: Heart failure as a consequence of sustained hemodynamic overload is among the most prevalent diseases in developed countries. The aim of the present study was to investigate the specific role of endothelial nitric oxide synthase (eNOS) in pressure overload-induced left ventricular (LV) hypertrophy.

Methods and results: Chronic pressure-overload LV hypertrophy was induced by abdominal aortic banding (AC) in wild-type (WT) and eNOS^−/− mice. Six weeks after abdominal AC, the consequences of the sustained pressure overload on LV morphology and function were noninvasively and invasively assessed using echocardiography and a 1.4 F conductance catheter. Sham-operated eNOS^−/− mice had significantly increased systolic blood pressure, slightly enhanced systolic function (preload recruitable stroke work) and normal diastolic function but no evidence of left ventricular hypertrophy when compared to sham-operated WT animals. AC resulted in a greater increase in anterior wall thickness in eNOS^−/− mice (0.8 ± 0.03 mm) compared to WT mice (0.7 ± 0.03 mm; P<0.05). The LV end-diastolic diameter was unchanged by AC in eNOS^−/− mice (sham: 3.8 ± 0.1 mm, AC: 3.7 ± 0.2 mm) but significantly increased in WT mice (sham: 3.9 ± 0.1 mm, AC: 4.5 ± 0.2 mm; P<0.05). Interstitial fibrosis and myocyte hypertrophy were greater in eNOS^−/− than in WT mice after AC. AC in eNOS^−/− mice caused a greater diastolic than systolic dysfunction compared to WT mice.

Conclusion: Chronic pressure overload in eNOS^−/− mice results in concentric LV hypertrophy without LV dilation and impaired systolic and diastolic function. These findings suggest that eNOS limits LV remodeling and dysfunction and modulates extracellular matrix proteins under chronic pressure overload.