Basal release of nitric oxide augments the Frank-Starling response in the isolated heart

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.

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 N(G)-monomethyl-L-arginine (L-NMMA, 10 micromol/L; n=10) or free hemoglobin (1 micromol/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 micromol/L; n=6). These changes were not attributable to alterations in coronary flow. Prostaglandin F2alpha (0.01 micromol/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 micromol/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.

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.