Endothelial nitric oxide synthase increases in left atria of dogs with pacing-induced heart failure.
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 NO-x 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.
Khadour
F H
FH
Department of Pharmacology, Cardiovascular Research Group, University of Alberta, Edmonton, Alberta, Canada T6G 2S2.
O'Brien
D W
DW
Fu
Y
Y
Armstrong
P W
PW
Schulz
R
R
D000818:Animals; D015153:Blotting, Western; D002304:Cardiac Pacing, Artificial; D003404:Creatinine / Q000097:blood; D003720:Densitometry; D004285:Dogs; D006325:Heart Atria; D006333:Heart Failure / Q000209:etiology / Q000378:metabolism*; D006352:Heart Ventricles; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009566:Nitrates / Q000097:blood; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III; D009573:Nitrites / Q000097:blood
D009566:Nitrates; D009573:Nitrites; D003404:Creatinine; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III