Inhibition of NO production increases myocardial blood flow and oxygen consumption in congestive heart failure.
Coronary blood flow (CBF) and myocardial oxygen consumption (MVO(2)) are reduced in dogs with pacing-induced congestive heart failure (CHF), which suggests that energy metabolism is downregulated. Because nitric oxide (NO) can inhibit mitochondrial respiration, we examined the effects of NO inhibition on CBF and MVO(2) in dogs with CHF. CBF and MVO(2) were measured at rest and during treadmill exercise in 10 dogs with CHF produced by rapid ventricular pacing before and after inhibition of NO production with N(G)-nitro-L-arginine (L-NNA, 10 mg/kg iv). The development of CHF was accompanied by decreases in aortic and left ventricular (LV) systolic pressure and an increase in LV end-diastolic pressure (25 +/- 2 mmHg). L-NNA increased MVO(2) at rest (from 3.07 +/- 0.61 to 4.15 +/- 0.80 ml/min) and during exercise; this was accompanied by an increase in CBF at rest (from 31 +/- 2 to 40 +/- 4 ml/min) and during exercise (both P < 0.05). Although L-NNA significantly increased LV systolic pressure, similar increases in pressure produced by phenylephrine did not increase MVO(2). The findings suggest that NO exerts tonic inhibition on respiration in the failing heart.
Traverse
Jay H
JH
Division of Cardiology, Department of Medicine, University of Minnesota Medical School, Minneapolis 55455, USA.
Chen
Yingjie
Y
Hou
Mingxiao
M
Bache
Robert J
RJ
D000818:Animals; D001011:Aorta; D002304:Cardiac Pacing, Artificial; D003326:Coronary Circulation; D003971:Diastole; D004285:Dogs; D004734:Energy Metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006333:Heart Failure / Q000209:etiology / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism*; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D010101:Oxygen Consumption / Q000187:drug effects; D005082:Physical Exertion; D013599:Systole; D016277:Ventricular Function, Left; D017725:Ventricular Pressure / Q000187:drug effects
D004791:Enzyme Inhibitors; D019335:Nitroarginine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase