(Circulation. 1997;96:1320-1329.)
© 1997 American Heart Association, Inc.
Articles |
Basal Release of Nitric Oxide Augments the Frank-Starling Response in the Isolated Heart
From the Department of Cardiology, Cardiovascular Sciences Group, University of Wales College of Medicine, Cardiff, UK (B.D.P., A.M.S.), and A.A. Bogomolets Institute of Physiology, Kiev, Ukraine (V.F.S.).
Correspondence to Dr A.M. Shah, Department of Cardiology, University of Wales College of Medicine, Heath Park, Cardiff, CF4 4XN, UK. E-mail shaham2{at}cf.ac.uk
Background The Frank-Starling response contributes to the regulation of cardiac output. The major underlying subcellular mechanism is a length-dependent change in myofilament responsiveness to Ca2+. Recent studies indicate that nitric oxide decreases myofilament responsiveness to Ca2+ and modulates myocardial relaxation and left ventricular (LV) diastolic function. We therefore investigated the interaction between nitric oxide and the Frank-Starling response.
Methods and Results Isolated ejecting guinea pig hearts
(constant afterload and heart rate) were studied before and after
interventions. Elevation of filling pressure from 10 to 20 cm
H2O increased cardiac output, LV end-diastolic
pressure (LVEDP), and peak LV pressure (LVPmax). In the
presence of
NG-monomethyl-L-arginine
(L-NMMA, 10 µmol/L; n=10) or free hemoglobin (1 µmol/L;
n=8), preload-induced increases in cardiac output were significantly
attenuated but baseline cardiac output was unaffected. The effects of
L-NMMA were inhibited in the presence of excess L-arginine
(100 µmol/L; n=6). These changes were not attributable to
alterations in coronary flow. Prostaglandin
F2
(0.01 µmol/L; n=6), which reduced
coronary flow, failed to alter the cardiac output response to
preload elevation. The exogenous nitric oxide donor sodium
nitroprusside (1 µmol/L; n=6) reduced cardiac output at the
lowest preload but not at higher preloads. LVEDP was elevated after
L-NMMA and hemoglobin but reduced after sodium nitroprusside.
Conclusions Basal intracardiac production of nitric oxide significantly augments preload-induced rises in cardiac output in the isolated ejecting guinea pig heart. The mechanism appears to be unrelated to changes in coronary flow and may involve direct effects of nitric oxide on myocardial diastolic and/or systolic function.
Key Words: endothelium-derived factors • myocardial contraction • cardiac output • ventricles
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