Nitric oxide mediates benefits of angiotensin II type 2 receptor overexpression during post-infarct remodeling.
We hypothesized that nitric oxide (NO) mediates the benefits of cardiac angiotensin II type 2 (AT(2)-R) overexpression during postmyocardial infarction (post-MI) remodeling. Eleven wild-type (WT) C57BL/6 mice and 28 transgenic (TG) mice with AT(2)-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 microL/g versus 2.53+/-0.14 microL/g in WT; 2.17+/-0.14 microL/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 AT(2)-R overexpression during post-MI remodeling.
Bove
Christina M
CM
University of Virginia Health System, Departments of Medicine and Radiology, Lee Street, Box 800170, Charlottesville, VA 22908, USA. ckramer@virginia.edu
Yang
Zequan
Z
Gilson
Wesley D
WD
Epstein
Frederick H
FH
French
Brent A
BA
Berr
Stuart S
SS
Bishop
Sanford P
SP
Matsubara
Hiroaki
H
Carey
Robert M
RM
Kramer
Christopher M
CM
D000818:Animals; D003094:Collagen / Q000032:analysis; D015870:Gene Expression; D006439:Hemodynamics; D008279:Magnetic Resonance Imaging; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D009206:Myocardium / Q000737:chemistry; D009569:Nitric Oxide / Q000502:physiology*; D044139:Receptor, Angiotensin, Type 2 / Q000235:genetics / Q000378:metabolism*; D020257:Ventricular Remodeling
D044139:Receptor, Angiotensin, Type 2; D009569:Nitric Oxide; D003094:Collagen