Endothelial NO formation does not control myocardial O2 consumption in mouse heart

To test whether endothelium-derived nitric oxide ( NO) regulates mitochondrial respiration, NO was pharmacologically modulated in isolated mouse hearts, which were perfused at constant flow to sensitively detect small changes in myocardial O-2 consumption (M(V)over dotO(2)). Stimulation of NO formation by 10 muM bradykinin (BK) increased coronary venous nitrite release fivefold to 58 +/- 33 nM (n = 17). Vasodilatation by BK, adenosine (1 muM), or papaverine (10 muM) decreased perfusion pressure, left ventricular developed pressure (LVDP), and M(V)over dotO(2). In the presence of adenosine-induced vasodilatation, stimulation of endothelial NO synthesis by BK had no effect on LVDP and M(V)over dotO(2). Also, inhibition of NO formation by N-G-monomethyl-L-arginine (L-NMMA, 100 muM) did not significantly alter LVDP and M(V)over dotO(2). Similarly, intracoronary infusion of authentic NO less than or equal to2 muM did not influence LVDP or M(V)over dotO(2) (-1 +/- 1%). Only when NO was >2 muM were contractile dysfunction and M(V)over dotO(2) reduction observed. Because BK-induced stimulation of endothelial NO formation and basal NO are not sufficient to impair M(V)over dotO(2) in the saline-perfused mouse heart, a tonic control of the respiratory chain by endothelial NO is difficult to conceive.