Endogenous basal nitric oxide production does not control myocardial oxygen consumption or function.

Previous studies from our laboratory have shown that an extrinsic nitric oxide (NO) donor (i.e., nitroprusside) caused vasodilatation and negative inotropy by activating guanylate cyclase and increasing myocardial cyclic GMP. We tested the hypothesis that endogenous myocardial NO production would limit myocardial oxygen consumption and function in vivo. We used the NO synthase inhibitors N(G)-nitro-L-arginine methyl ester (L-NAME) and N(G)-monomethyl-L-arginine (L-NMMA) in nine open-chest anesthetized mongrel dogs. Either L-NAME (6 mg/kg) or L-NMMA (3 mg/kg) were infused into the left anterior descending coronary artery (LAD). The circumflex (CFX) coronary artery region served as a control. Regional segment work was calculated as the integrated product of local force (miniature transducer) and segment shortening (ultrasonic crystals). Local myocardial O2 consumption was determined using an ultrasonic LAD flow probe and local arterial-venous O2 content difference (oximetry). Cyclic GMP levels were obtained via a radioimmunoassay. Both L-NAME and L-NMMA caused a local decrease in coronary blood flow (LAD flow: 80 +/- 8 to 69 +/- 7 ml/min/100 g [means +/- SEM]) and increased O2 extraction (9.1 +/- 0.6 to 10.2 +/- 0.7 ml O2/100 ml). However, this led to no change in local O2 consumption. LAD segment force was not altered (12.1 +/- 0.7 to 11.6 +/- 0.9 g), nor was the percent shortening changed (10.8 +/- 1.8% to 10.0 +/- 1.4%) by L-NAME or L-NMMA, leading to no net change in segment work. Myocardial cyclic GMP levels were not different in a comparison between the LAD (1.7 +/- 0.4 pmoles/g) and control (1.7 +/- 0.2) regions with either L-NAME or L-NMMA. We conclude that blockade of endogenous NO production with L-NAME and L-NMMA is sufficient to cause vasoconstriction in the heart of anesthetized dogs. However, this dose did not lead to alteration in local myocardial function, O2 consumption, or cyclic GMP levels.