Aging Blunts the Effect of Nitric Oxide on Myocardial O2 Consumption

penicillamine (SNAP, 10 -4 M, a nitric oxide donor) was applied to the left ventricle. Coronary blood flow (microspheres) and O2 extraction (microspectrophotometry) were used to determine subepicardial (EPI) and subendocardial (ENDO) O2 consumption. Wall thickening was determined ultrasonically. Cyclic GMP and guanylyl cyclase activity were determined. RESULTS. Myocardial O2 extraction, flow, O2 consumption and wall thickening were comparable in young and old hearts. The EPI and ENDO O2 consumption of the SNAP treated young hearts decreased significantly (>25%) compared to vehicle, Fig. 1 (left). However, SNAP had no significant effects on the O2 consumption of old hearts. SNAP also decreased the % wall thickening in the young (18.0±1.7 to 13.4±1.6%), but not old hearts (14.5±0.9 to 11.4%). The basal cyclic GMP levels in the old hearts were greater (~70%) than those in young hearts, Fig. 1 (right). SNAP increased cyclic GMP in EPI and ENDO of young, but not old, hearts. Guanylyl cyclase activity was assessed in both the young and old hearts at baseline and after increasing concentrations of sodium nitroprusside. Guanylyl cyclase activity was elevated in the old rabbit hearts with 0.5 mM nitroprusside (131±12 vs. 80±12 pmol/min/mg protein).