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Departments of 1 Pharmacology, 2 Medicine, and 3 Pediatrics, Cardiovascular Research Group, University of Alberta, Edmonton, Alberta, Canada T6G 2S2
In congestive heart failure (CHF) the
alterations in cardiac NO synthase (NOS) isoforms activity and
expression are incompletely documented and the chamber specificity of
these changes is unknown. We studied plasma nitrate-nitrite
(NO
x), atrial, and ventricular NOS
activities and protein expression (Western blot and densitometric
analysis) in nonpaced control dogs and in dogs paced for 2 or 21 days
into CHF. Plasma NOx rose
significantly after 7 and 21 days of pacing, whereas creatinine levels
remained unchanged. In control dogs
Ca2+-dependent NOS activity in
left atria was double that of right or left ventricular activity. In
paced animals the activity increased only in the atria after 21 but not
2 days of pacing. Levels of endothelial NOS (eNOS) protein were
enhanced in the left atria but not ventricles after 21 days of pacing
because of a greater quantity of the 150-kDa but not the 135-kDa eNOS.
Ca2+-independent NOS activity was
undetectable in any cardiac tissue. The specific upregulation of eNOS
in the left atria suggests that NO production may be enhanced to
counterbalance hypertrophy that develops during pacing-induced CHF.
congestive heart failure; atrial hypertrophy; nitrate-nitrite
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