Effect of NO on transmural distribution of blood flow in hypertrophied left ventricle during exercise.
When exercise in the presence of a coronary artery stenosis results in subendocardial ischemia, administration of a nitric oxide (NO) donor increases subendocardial blood flow, whereas NO synthesis blockade worsens subendocardial hypoperfusion. Because left ventricular hypertrophy (LVH) is also associated with subendocardial hypoperfusion during exercise, this study tested the hypothesis that alterations of NO availability can similarly influence subendocardial blood flow in the hypertrophied heart. Studies were performed in seven dogs in which ascending aortic banding resulted in an 80% increase in LV weight. Myocardial blood flow was measured with microspheres during treadmill exercise that increased heart rates to 216 +/- 8 beats/min. During control exercise, mean myocardial blood flow in animals with LVH was similar to that in historic controls, but the ratio of subendocardial to subepicardial blood flow was lower in animals with hypertrophy (0.88 +/- 0.07) than in controls (1.36 +/- 0.08; P < 0.05). Blockade of NO synthesis with NG-nitro-L-arginine (L-NNA; 1.5 mg/kg ic) caused no change in heart rate or LV systolic pressure during exercise. Furthermore, L-NNA did not worsen subendocardial hypoperfusion during exercise. Intracoronary infusion of nitroglycerin (0.4 microgram. kg-1. min-1) did not significantly alter either mean blood flow or the transmural distribution of perfusion during exercise in the hypertrophied hearts. Thus, unlike the subendocardial underperfusion that occurs when a stenosis limits coronary blood flow, alterations of NO availability did not alter subendocardial hypoperfusion in the hypertrophied hearts.
Duncker
D J
DJ
Cardiology Division, Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota 55455, USA.
Traverse
J H
JH
Ishibashi
Y
Y
Bache
R J
RJ
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects*; D004285:Dogs; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D017379:Hypertrophy, Left Ventricular / Q000503:physiopathology*; D009043:Motor Activity / Q000502:physiology*; D009569:Nitric Oxide / Q000494:pharmacology*; D019335:Nitroarginine / Q000494:pharmacology; D005996:Nitroglycerin / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D004791:Enzyme Inhibitors; D014665:Vasodilator Agents; D019335:Nitroarginine; D009569:Nitric Oxide; D005996:Nitroglycerin