ENDOGENOUS BASAL NITRIC-OXIDE PRODUCTION DOES NOT CONTROL MYOCARDIAL OXYGEN-CONSUMPTION OR FUNCTION

Previous studies from our laboratory have shown that an extrinsic nitr ic oxide (NO) donor (i.e., nitroprusside) caused vasodilatation and ne gative inotropy by activating guanylate cyclase and increasing myocard ial cyclic GMP, We tested the hypothesis that endogenous myocardial NO production would limit myocardial oxygen consumption end function in vivo, We used the NO synthase inhibitors N-G-nitro-L-arginine methyl e ster (L-NAME) and N-G-monomethyl-L-arginine (L-NMMA) in nine open-ches t anesthetized mongrel dogs, Either L-NAME (6 mg/kg) or L-NMMA (3 mg/k g) were infused into the left anterior descending coronary artery (LAD ). The circumflex (CFX) coronary artery region served as a control. Re gional segment work was calculated as the integrated product of local force (miniature transducer) and segment shortening (ultrasonic crysta ls), Local myocardial O-2 consumption was determined using an ultrason ic LAD flow probe and local arterial-venous O-2 content difference (ox imetry), 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 O-2 extraction (9.1 +/- 0.6 to 10.2 +/- 0.7 mi O-2/100 ml). However, this led to no change in local 0, consumption. LAD segment force was n ot altered (12.1 +/- 0.7 to 11.6 +/- 0.9 g), nor was the percent short ening changed (10.8 +/- 1.8% to 10.0 +/- 1.4%) by L-NAME or L-NMMA, le ading to no net change in segment work, Myocardial cyclic GMP levels w ere 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-N MMA is sufficient to cause vasoconstriction in the heart of anesthetiz ed dogs, However, this dose did not lead to alteration in local myocar dial function, O-2 consumption, or cyclic GMP levels.