FUNCTION AND PRODUCTION OF NITRIC-OXIDE IN THE CORONARY CIRCULATION OF THE CONSCIOUS DOG DURING EXERCISE

This study determined the changes in NO production from the coronary c irculation of the conscious dog during exercise. The role of endogenou s NO as it relates to coronary flow, myocardial work, and metabolism w as also studied. Mongrel dogs were chronically instrumented for measur ements of coronary blood flow (CBF), ventricular and aortic pressures, and ventricular diameter, with catheters in the aorta and coronary si nus. Acute exercise (5 minutes at 3.6, 5.9, and 9.1 mph) was performed , and hemodynamic measurements and blood samples were taken at each ex ercise level. Nitro-L-arginine (NLA, 35 mg/kg IV) was given to block N O synthesis, and the exercise was repeated. Blood samples were analyze d for oxygen, plasma nitrate/nitrite Can index of NO), lactate, glucos e, and free fatty acid (FFA) levels. Acute exercise caused significant elevations in NO production by the coronary circulation (46+/-23, 129 +/-44, and 63+/-32 nmol/min at each speed respectively, P<.05). After NLA, there was no measurable NO production at rest or during exercise. Blockade of NO synthesis resulted in elevations in myocardial oxygen consumption and reductions in myocardial FFA consumption for comparabl e levels of CBF and cardiac work. The metabolic changes after NLA occu rred in the absence of alterations in myocardial lactate or glucose co nsumptions. NO production by the coronary circulation is increased wit h exercise and blocked by NLA. The absence of NO in the coronary circu lation during exercise does not affect levels of CBF, because it shift s the relationship between cardiac work and myocardial oxygen consumpt ion, suggesting that endogenous NO modulates myocardial metabolism.