nNOS Gene Deletion Exacerbates Pathological Left Ventricular Remodeling and Functional Deterioration After Myocardial Infarction

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Abstract
Background— The neuronal isoform of nitric oxide synthase (nNOS) has been implicated in the regulation of basal and β-adrenergic inotropy in normal and chronically infarcted hearts. Furthermore, myocardial nNOS expression and activity increase in failing hearts, raising the possibility that nNOS may influence left ventricular (LV) remodeling progression and functional deterioration after myocardial infarction (MI) Methods and Results— We compared LV remodeling at 1, 4, and 8 weeks after MI in nNOS-knockout mice (nNOS−/−) and their wild-type (WT) littermates matched for infarct size by using a highly accurate 3-dimensional echocardiographic technique. Basal LV hemodynamics and the inotropic response to dobutamine infusion (4 and 16 ng · g−1 · min−1) were also evaluated 8 weeks after MI. Sham-operated nNOS−/− mice showed enhanced basal LV contractility (P<0.03 versus WT, as evaluated by preload-recruitable stroke work) but an attenuated inotropic response to dobutamine infusion (P<0.01 versus WT). Both basa...