Reduced synthesis of NO causes marked alterations in myocardial substrate metabolism in conscious dogs.
To test whether the acute reduction of nitric oxide (NO) synthesis causes changes in cardiac substrate metabolism and in the activity of key enzymes of fatty acid and glucose oxidation, we blocked NOS by giving N(omega)-nitro-L-arginine methyl ester (L-NAME; 35 mg/kg iv two times) to nine chronically instrumented dogs. [3H]oleate, [14C]glucose, and [13C]lactate were infused to measure the rate of cardiac substrate uptake and oxidation. Glyceraldehyde-3-phosphate dehydrogenase, acetyl-CoA carboxylase, and malonyl-CoA decarboxylase activities were measured in myocardial biopsies. In eight control dogs, ANG II was infused (20-40 ng x kg(-1) x min(-1)) to mimic the hemodynamic effects of L-NAME. After L-NAME, significant changes occurred for fatty acid oxidation (from 9.8 +/- 0.8 to 7.1 +/- 1.2 micromol/min), glucose uptake (from 12.9 +/- 5.5 to 45.0 +/- 14.2 micromol/min), and oxidation (from 4.4 +/- 1.2 to 19.9 +/- 2.3 micromol/min). ANG caused only a significantly lower increase in glucose oxidation. Lactate uptake increased by more than twofold in both groups. The enzyme activities did not differ significantly between the two groups. In conclusion, the acute inhibition of NO synthesis causes marked metabolic alterations that do not involve key rate-controlling enzymes of fatty acid oxidation nor glyceraldehyde-3-phosphate dehydrogenase.
Recchia
Fabio A
FA
Department of Physiology, New York Medical College, Valhalla, New York 10595, USA. fabio_recchia@nymc.edu
Osorio
Juan Carlos
JC
Chandler
Margaret P
MP
Xu
Xiaobin
X
Panchal
Ashish R
AR
Lopaschuk
Gary D
GD
Hintze
Thomas H
TH
Stanley
William C
WC
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D004285:Dogs; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005227:Fatty Acids / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006439:Hemodynamics / Q000187:drug effects; D019344:Lactic Acid / Q000378:metabolism; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D010084:Oxidation-Reduction / Q000187:drug effects
D004791:Enzyme Inhibitors; D005227:Fatty Acids; D000804:Angiotensin II; D009569:Nitric Oxide; D019344:Lactic Acid; D005947:Glucose; D019331:NG-Nitroarginine Methyl Ester