Circulation. 2001;104:1286-1291
doi: 10.1161/hc3601.094298
doi: 10.1161/hc3601.094298
(Circulation. 2001;104:1286.)
© 2001 American Heart Association, Inc.
Basic Science Reports |
Endothelial Nitric Oxide Synthase Limits Left Ventricular Remodeling After Myocardial Infarction in Mice
From the Cardiology Division (M.S.-C., K.D.B., A.-C.V., P.L.H., M.H.P.) and the Cardiovascular Research Center (K.D.B., H.N., P.L.H.) of the Department of Medicine, the Department of Anesthesia and Critical Care (R.U., W.M.Z.), the Department of Pathology (H.T.A.), and the Department of Surgery (B.N.) at Massachusetts General Hospital, and the Cardiovascular Division (M.L.L., R.T.L.) of the Department of Medicine at Brigham and Women Hospital and Harvard Medical School, Boston, Mass.
Correspondence to Marielle Scherrer-Crosbie, MD, Cardiac Ultrasound Laboratory, Massachusetts General Hospital, 32 Fruit Street, Boston, MA 02114. E-mail marielle{at}crosbie.com
Background— To investigate the role of endothelial nitric oxide synthase (NOS3) in left ventricular (LV) remodeling after myocardial infarction (MI), the impact of left anterior descending coronary artery ligation on LV size and function was compared in 2- to 4-month-old wild-type (WT) and NOS3-deficient mice (NOS3-/-).
Methods and Results— Two days after MI, both strains of mice had a similar LV size, fractional shortening, and ejection fraction by echocardiography. Twenty-eight days after MI, both strains had dilated LVs with decreased fractional shortening and lower ejection fractions. Although the infarcted fraction of the LV was similar in both strains, LV end-diastolic internal diameter, end-diastolic volume, and mass were greater, but fractional shortening, ejection fraction, and the maximum rate of developed LV pressure (dP/dtmax) were lower in NOS3-/- than in WT mice. Impairment of diastolic function, as measured by the time constant of isovolumic relaxation (
) and the maximum rate of LV pressure decay (dP/dtmin), was more marked in NOS3-/- than in WT mice. Mortality after MI was greater in NOS3-/- than in WT mice. Long-term administration of hydralazine normalized blood pressure in NOS3-/- mice, but it did not prevent the LV dilatation, impaired systolic and diastolic function, and increased LV mass that followed MI. In WT mice, capillary density and myocyte width in the nonischemic portion of the LV did not differ before and 28 days after MI, whereas in NOS3-/- mice, capillary density decreased and myocyte width increased after MI, whether or not hydralazine was administered.
Conclusions— These results suggest that the presence of NOS3 limits LV dysfunction and remodeling in a murine model of MI by an afterload-independent mechanism, in part by decreasing myocyte hypertrophy in the remote myocardium.
Key Words: echocardiography • ventricles • hypertrophy
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