Endogenous endothelial nitric oxide synthase-derived nitric oxide is a physiological regulator of myocardial oxygen consumption

Our objective was to determine the precise role of endothelial nitric oxide synthase (eNOS) as a modulator of cardiac O-2 consumption and to further e xamine the role of nitric oxide (NO) in the control of mitochondrial respir ation. Left ventricle O-2 consumption in mice with defects in the expressio n of eNOS [eNOS (-/-)] and inducible NOS [iNOS (-/-)] was measured with a C lark-type O-2 electrode. The rate of decreases in O-2 concentration was exp ressed as a percentage of the baseline. Baseline O-2 consumption was not si gnificantly different between groups of mice, Bradykinin (10(-4) mol/L) ind uced significant decreases in O-2 consumption in tissues taken from iNOS (- /-) (-28+/-4%), wild-type eNOS (+/+) (-22+/-4%), and heterozygous eNOS(+/-) (-22+/-5%) but not homozygous eNOS (-/-) (-3+/-4%) mice. Responses to brad ykinin in iNOS (-/-) and both wild-type and heterozygous eNOS mice were att enuated after NOS blockade with N-nitro-L-arginine methyl eater (L-NAME) (- 2+/-5%, -3+/-2% and -6+/-5%, respectively, P<0.05). In contrast, S-nitroso- N-acetyl-penicillamine (SNAP, 10-4 mol/L), which releases NO spontaneously, induced decreases in myocardial O-2 consumption in all groups of mice, and such responses were not affected by L-NAME. In addition. pretreatment with bacterial endotoxin elicited a reduction in basal O-2 consumption in tissu es taken from normal but not iNOS (-/-)-deficient mice. Our results indicat e that the pivotal role of eNOS in the control of myocardial O-2 consumptio n and modulation of mitochondrial respiration by NO may have an important r ole in pathological conditions such as endotoxemia in which the production of NO is altered.