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Reversible Myocardial Dysfunction in Alcohol Fed Rats Mediated by Nitric Oxide Synthase
Author(s) -
Khanna Deepak,
kan Hong,
Fang Qiujuan,
Xie Zirong,
Underwood Brandi L,
Jain Abnash C,
Finkel Mitchell S
Publication year - 2007
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.21.6.a1255-a
Subject(s) - medicine , endocrinology , ventricle , alcohol , nitric oxide , nitric oxide synthase , diastole , blood pressure , hemodynamics , ingestion , ventricular pressure , ethanol , chemistry , biochemistry
We sought to characterize the hemodynamic effects of chronic alcohol ingestion in awake rats and elucidate the cellular mechanisms contributing to alcohol induced myocardial dysfunction. Adult male rats were fed a diet containing either ethanol (13gm/kg/day) or isocaloric control diet for one month. Blood alcohol level was 177.5¡À18.1mg/dL. In vivo hemodynamics were measured by a catheter tip in the left ventricle. In alcohol treated rats, the left ventricular end diastolic pressure was increased (6.3¡À0.8 vs 3.2¡À0.8 mmHg in control, n=12; p<0.05) and the systolic developed left ventricular pressure was decreased (168¡À6 vs 197¡À5 mmHg in control, n=12; p<0.05). Alcohol fed rats revealed depressed systolic and diastolic function (+dp/dt =10847 ¡À326 vs 12689¡À397 in control; n=12; p<0.01), (−dp/dt = 8989 ¡À380 vs 10468¡À397 in control; n=12; p<0.01). Alcohol ingestion was associated with iNOS protein synthesis by Western. Cardiac myocytes isolated from alcohol‐fed rats demonstrated an attenuated response to increasing concentrations of the beta adrenergic agonist, isoproterenol (10–9−10–7 M), (p<0.01; n=25cells/5rats) compared to controls. This response was significantly reversed by the iNOS inhibitor, L‐NMMA. Alcohol ingestion results in iNOS mediated attenuation of adrenergic signaling and depression in both systolic and diastolic function in rats.