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(Hypertension. 2004;43:680.)
© 2004 American Heart Association, Inc.

Scientific Contributions

Nitric Oxide Mediates Benefits of Angiotensin II Type 2 Receptor Overexpression During Post-Infarct Remodeling

Christina M. Bove; Zequan Yang; Wesley D. Gilson; Frederick H. Epstein; Brent A. French; Stuart S. Berr; Sanford P. Bishop; Hiroaki Matsubara; Robert M. Carey; Christopher M. Kramer

From Departments of Medicine (C.M.B., R.M.C., C.M.K.), Radiology (F.H.E., B.A.F., S.S.B., C.M.K.), and Biomedical Engineering (Z.Y., W.D.G., F.H.E., B.A.F., S.S.B.), University of Virginia, Charlottesville; Department of Pathology (S.P.B.), University of Alabama, Birmingham; and Department of Cardiovascular Medicine (H.M.), Kyoto Prefectural University School of Medicine, Kyoto, Japan.

Correspondence to Dr Christopher M. Kramer, University of Virginia Health System, Departments of Medicine and Radiology, Lee Street, Box 800170, Charlottesville, VA 22908. E-mail ckramer{at}virginia.edu

We hypothesized that nitric oxide (NO) mediates the benefits of cardiac angiotensin II type 2 (AT₂-R) overexpression during postmyocardial infarction (post-MI) remodeling. Eleven wild-type (WT) C57BL/6 mice and 28 transgenic (TG) mice with AT₂-R overexpression were studied by cardiac magnetic resonance imaging (CMR) at baseline and days 1 and 28 post-MI induced by left anterior descending artery occlusion and reperfusion. Sixteen TG mice were treated from day 1 through 28 post-MI with the NO synthase inhibitor N^G-nitro-L-arginine methyl ester in drinking water at 1 mg/mL (TG-Rx). Left ventricular mass index (LVMI), end-diastolic volume index (EDVI) and end-systolic volume index (ESVI), wall thickness, percent thickening, and ejection fraction (EF) were measured. Infarct size on day 1 was assessed by post-contrast CMR. Interstitial collagen was quantified in noninfarcted regions. At baseline, heart rate (HR), blood pressure (BP), LVMI, EDVI, and ESVI were similar between groups, as were infarct size and weekly post-MI HR and systolic BP. By day 28 post-MI, EDVI and ESVI were similar in WT and TG-Rx, but significantly lower in TG (ESVI: 1.41±0.18 µL/g versus 2.53±0.14 µL/g in WT; 2.17±0.14 µL/g in TG-Rx; P<0.008 for both). At day 28, EF was higher in TG (46.3%±2.9%) compared with WT and TG-Rx (32.7±2.3% and 33.7±2.3, respectively; P<0.003 for both). Wall thickening at day 28 post-MI was greater in the base and mid-LV in TG than WT and TG-Rx. Noninfarcted region interstitial collagen was similar between groups. Thus, the NO pathway may mediate much of the benefits of cardiac AT₂-R overexpression during post-MI remodeling.

Key Words: angiotensin • MRI • myocardial infarction • remodeling • nitric oxide • receptors • imaging

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