Endogenous nitric oxide enhances coupling between O-2 consumption and ATP synthesis in guinea pig hearts

Endogenous nitric oxide (eNO) modulates tissue respiration. To test whether eNO modulates myocardial O-2 consumption (M(V) over dot O-2), ATP synthesi s, and metabolic efficiency, we used isolated isovolumic guinea pig hearts perfused at a constant flow. N-omega-nitro-L-arginine (L-NNA; 5 x 10(-5) mo l/l) was used to inhibit eNO production. M(V) over dot O-2 was measured at different levels of cardiac work, estimated as the rate-pressure product (R PP). ATP content and synthesis rate were determined using P-31 NMR and magn etization transfer during high cardiac work. L-NNA increased coronary vascu lar resistance (19 +/- 3%, P< 0.05) and M(V) over dot O-2 (12 +/- 3%, P< 0. 05) without an increase in the RPP. In contrast, vehicle infusion resulted in insignificant changes in coronary vascular resistance (3 +/- 2%, P> 0.05 ) and M(V) over dot O-2 (-2 +/- 1%, P< 0.05). Compared with vehicle, L-NNA caused a higher M(V) over dot O-2 both during KCl arrest (L-NNA 5.6 +/- 0.5 vs. vehicle 3.0 +/- 0.4 <mu>mol . min(-1) . mg dry wt(-1), P< 0.05) and du ring increased cardiac work elicited by elevating perfusate Ca2+, indicatin g an upward shift in the relationship between contractile performance (meas ured as RPP) and M(V) over dot O-2. However, neither ATP contents nor ATP s ynthesis rates were different in the two groups during high cardiac work. T hus, because inhibition of eNO production by L-NNA increased M(V) over dot O-2 without a change in the ATP synthesis rate, these data suggest that eNO increases myocardial metabolic efficiency by reducing M(V) over dot O-2 in the heart.