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Role of iNOS in Intrinsic Myocyte Dysfunction during Progression of Left Ventricular Hypertrophy
Author(s) -
Kim SongJung,
Chavez Jaime,
Crystal George J.
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.596.1
Subject(s) - medicine , left ventricular hypertrophy , cardiology , myocyte , muscle hypertrophy , diastole , nitric oxide synthase , nitric oxide , endocrinology , blood pressure
Our objective was to assess the role of inducible nitric oxide synthase (iNOS) in the intrinsic myocyte dysfunction in the compensated and uncompensated stages of left ventricular hypertrophy (LVH). 19 dogs were divided into three groups, Control (CON; n =7), LVH (n=7), and LVH/HF (n= 5), and instrumented for measurements of hemodynamics and LV function. LVH was induced by chronic aortic banding. Progression into LVH/HF was achieved by rapid ventricular pacing. Cardiac myocytes were isolated so that intrinsic contractile function (percent contraction; %C) could be assessed by video imaging. LV systolic pressure and wall stress, and LV wall thickness were increased 2‐fold in LVH compared to CON. LV end‐diastolic pressure was increased 4‐fold and LV dP/dt max was decreased by 30% in LVH compared to LVH/HF. %C was reduced by 30 % in LVH compared CONT (9.4±0.3%). However, in similarity to CON, 1 mM L‐arginine (the substrate for iNOS) caused no change in %C in LVH. Furthermore, expression of iNOS (Western blot) was not increased in LVH relatve to CON. %C was further reduced in LVH/HF. In contrast to LVH, L‐arginine caused marked decrease in %C in LVH/HF, which was blunted by specific iNOS inhibitor AMT. iNOS expression was increased more than 3‐fold in LVH/HF. Taken together, our results suggest that iNOS does not play a role in the intrinsic myocyte dysfunction during compensated LVH, but does so during the uncompensated stage.