Mechanisms of nitrate accumulation in plasma during pacing-induced heart failure in conscious dogs.
The goal of this study was to understand the mechanisms behind the changes in plasma NOx during heart failure. Heart failure is associated with an increase in plasma nitrate levels, and yet most experimental evidence demonstrates a reduction in endothelial nitric oxide production during heart failure. Dogs were chronically instrumented for measurement of systemic hemodynamics and left ventricular (LV) dimensions. Hearts were paced at 210 bpm for 3 weeks (n = 14) and then 240 bpm for 1 week (n = 7). Hemodynamics, arterial blood gases, plasma NOx, and creatinine levels were monitored weekly. Heart failure was evidenced by cachexia, ascites, and hemodynamic alterations. Resting heart rate rose (94 +/- 6 to 135 +/- 9 bpm), and LV dP/dt fell (2810 +/- 82 to 1471 +/- 99 mm Hg/s), while LV end diastolic pressure quadrupled (5.8 +/- 0.7 to 25 +/- 0.8 mm Hg), and diastolic wall stress quadrupled (11 +/- 1.3 to 43 +/- 6.0 g/cm2, all P < 0.05). These changes occurred during a doubling in plasma NOx (5.5 +/- 1.5 to 10 +/- 1.6 microM, P < 0.05). There were no changes in plasma NOx through 3 weeks of pacing. Plasma creatinine levels increased 450% (from 0.27 +/- 0.32 to 1.21 +/- 0.63 mg%). Stimulated nitrite production by agonists in sieved coronary microvessels was unchanged after 3 weeks of pacing but was reduced after heart failure. Plasma NOx did not correlate with LV dP/dt or systolic wall stress but correlated directly with LV EDP or diastolic wall stress and inversely with cardiac work. Plasma NOx rose in direct relation to plasma creatinine levels (Y = 4.8X + 2.8, r2 = 0.84), suggesting that the rise in plasma NOx during heart failure is due to decreased renal function not increased NO production.
Bernstein
R D
RD
Department of Physiology, New York Medical College, Valhalla 10595, USA.
Zhang
X
X
Zhao
G
G
Forfia
P
P
Tuzman
J
J
Ochoa
F
F
Ochoa
M
M
Vogel
T
T
Hintze
T H
TH
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure; D001920:Bradykinin / Q000494:pharmacology; D002245:Carbon Dioxide / Q000097:blood; D002304:Cardiac Pacing, Artificial; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D004285:Dogs; D006321:Heart / Q000503:physiopathology*; D006333:Heart Failure / Q000097:blood* / Q000503:physiopathology*; D006339:Heart Rate; D006439:Hemodynamics; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology; D009566:Nitrates / Q000097:blood*; D009573:Nitrites / Q000097:blood; D010100:Oxygen / Q000097:blood; D010313:Partial Pressure; D012044:Regression Analysis; D016277:Ventricular Function, Left
D009566:Nitrates; D009573:Nitrites; D002245:Carbon Dioxide; D000109:Acetylcholine; D010100:Oxygen; D001920:Bradykinin