Nitric oxide controls cardiac substrate utilization in the conscious dog

Objectives: The aim of this study was to determine whether the acute inhibi tion of nitric oxide (NO) synthase causes changes in cardiac substrate util ization which can be reversed by a NO donor. Methods: NO synthase was block ed by giving 30 mg/kg of nitro-L-arginine (NLA) i.v. to 15 chronically inst rumented dogs. Hemodynamics and blood samples from aorta and coronary sinus were taken at control and at 1 and 2 h after NLA. In five dogs, 0.4 mg/kg of the NO donor 3754 was given i.v. 1 h after NLA. In six dogs, angiotensin II was infused over 2 h (20-40 ng/kg/min) to mimic the hemodynamic effects of NLA. Results: Two h after NLA: mean arterial pressure was 153+/-4 mmHg; MVO2 increased by 38%; cardiac uptake of lactate and glucose increased, re spectively, from 20.0+/-5.0 to 41.0+/-9.3 mu mol/min and from 1.1+/-0.7 to 6.8+/-1.5 mg/min (all P<0.05 vs. control). Cardiac uptake of free fatty aci ds decreased by 43% after 1 h (P<0.05) and returned to control values at 2 h. Cardiac respiratory quotient increased from 0.76+/-0.03 to 1.05+/-0.07, indicating a shift to carbohydrate oxidation. All these changes were revers ed by the NO donor. In the dogs receiving angiotensin II infusion, MVO2 inc reased by 28% and lactate uptake doubled (both P<0.05), but no other metabo lic changes where observed. Conclusions: The acute inhibition of NO synthas e by NLA causes a switch from fatty acids to lactate and glucose utilizatio n by the heart which can be reversed by a NO donor, suggesting an important regulatory action of NO on cardiac metabolism. (C) 1999 Published by Elsev ier Science B.V. All rights reserved.