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1 Department of Physiology, New York Medical College, Valhalla, New York 10595; 2 Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio 44106; and 3 Heritage Medical Research Centre, University of Alberta, Edmonton, Canada T6G 2S2
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
-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 · kg
1 · 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 µmol/min), glucose
uptake (from 12.9 ± 5.5 to 45.0 ± 14.2 µmol/min), and
oxidation (from 4.4 ± 1.2 to 19.9 ± 2.3 µmol/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.
fatty acids; glucose; lactate; oxidation; heart
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