© 1999 by European Society of Cardiology
Copyright © 1999, European Society of Cardiology
Nitric oxide controls cardiac substrate utilization in the conscious dog
Department of Physiology, New York Medical College, Valhalla, NY 10595, USA
* Corresponding author. Tel.: +1-914-594-3633; fax: +1-914-594-4018 Thomas_Hintze{at}nymc.edu
Objectives: The aim of this study was to determine whether the acute inhibition of nitric oxide (NO) synthase causes changes in cardiac substrate utilization which can be reversed by a NO donor. Methods: NO synthase was blocked by giving 30 mg/kg of nitro-L-arginine (NLA) i.v. to 15 chronically instrumented 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, respectively, from 20.0±5.0 to 41.0±9.3 µmol/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 acids 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 reversed by the NO donor. In the dogs receiving angiotensin II infusion, MVO2 increased by 28% and lactate uptake doubled (both P<0.05), but no other metabolic changes where observed. Conclusions: The acute inhibition of NO synthase by NLA causes a switch from fatty acids to lactate and glucose utilization by the heart which can be reversed by a NO donor, suggesting an important regulatory action of NO on cardiac metabolism.
KEYWORDS Energy metabolism; Hemodynamics; Nitric oxide; Oxygen consumption
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