Premium
Beneficial effect of eNOS overexpression on pressure overload induced cardiac hypertrophy and dysfunction unmasked by ROS scavenging
Author(s) -
Deel Elza Dianne,
Boer Martine,
Merkus Daphne,
Haperen Rien,
Crom Rini,
Duncker Dirk Jan
Publication year - 2011
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.25.1_supplement.1093.9
Subject(s) - enos , pressure overload , medicine , reactive oxygen species , nitric oxide , cardiology , endocrinology , muscle hypertrophy , oxidative stress , left ventricular hypertrophy , chemistry , heart failure , nitric oxide synthase , blood pressure , biochemistry , cardiac hypertrophy
Although initiated as a compensatory mechanism, left ventricular hypertrophy (LVH) resulting from pressure overload increases the risk for heart failure. Nitric Oxide (NO) constitutes an important protective molecule against LVH possibly in part by its ability to scavenge reactive oxygen species (ROS). We previously showed NO to be protective after myocardial infarction. However, whether additional NO attenuates pressure overload LVH and the role therein of reducing ROS levels, is currently unknown. Consequently, we studied the effect of endothelial NO synthase (eNOS) overexpression on LVH and left ventricular (LV) function after transverse aortic constriction (TAC) in mice in the absence and the presence of the ROS scavenger N ‐acetyl cysteine. In wildtype mice, TAC induced marked LVH, LV dysfunction and pulmonary congestion. eNOS overexpression had no effect on LV geometry and function in sham‐operated animals and surprisingly failed to protect against overload induced LVH while even aggravating LV dysfunction. Scavenging of ROS, which had no beneficial effects in wildtype TAC mice, reduced LVH and pulmonary congestion and improved LV function in eNOS transgenic TAC mice. In conclusion, eNOS overexpression increases rather than reduces ROS levels after TAC, possibly as a result of eNOS uncoupling. Consequently, ROS scavenging unmasked the beneficial effects of eNOS. Supported by NHF grant 2007B024