(Circulation. 1997;96:3436-3442.)
© 1997 American Heart Association, Inc.
Articles |
Left Ventricular Contractile Effects of Inducible Nitric Oxide Synthase in the Human Allograft
From the Cardiovascular Center, OLV Ziekenhuis, Aalst, Belgium (W.J.P., P.P., M.V.); the Department of Cardiology, University of Wales College of Medicine, Cardiff, UK (A.M.S); and Abteilung Kardiologie, Medizinische Hochschule, Hannover, Germany (S.K., H.D.).
Correspondence to Dr Walter J. Paulus, MD, PhD, Cardiovascular Center, OLV Ziekenhuis, Moorselbaan 164, B 9300 Aalst, Belgium. E-mail Walter.Paulus{at}ping.be
Background Myocardial expression of inducible (i) nitric oxide (NO) synthase (iNOS) gene has been reported in transplant recipients and in dilated cardiomyopathy. NO derived from NO donor or from coronary endothelium has previously been shown in the human heart to reduce end-systolic left ventricular (LV) pressure, especially during ß-adrenoreceptor stimulation, because of earlier onset of LV relaxation. The present study investigated in transplant recipients whether a similar cardiodepressant effect could be attributed to NO derived from iNOS.
Methods and Results In 16 transplant recipients who were free of
rejection or graft vasculopathy, microtip LV pressure
recordings, LV angiograms, and
endomyocardial biopsies were obtained at annual
coronary angiography. In 8 transplant recipients, microtip LV
pressure recordings were obtained during
intravenous dobutamine(5 µg ·
kg-1 · min-1). Competitive reverse
transcription–polymerase chain reaction of iNOS mRNA was performed on
the endomyocardial biopsies, and the intensity of
iNOS mRNA expression was quantified on a scale ranging from 0 to 5+.
All measures of baseline LV function were comparable in transplant
recipients with low (
2+) or high myocardial iNOS mRNA. During
intravenous dobutamine infusion, there was a
significant correlation between the abbreviation of LV
electromechanical systole time (LVEST is the time from onset of QRS
to dP/dtmin) and the rise of LV dP/dtmax
(r=.79; P<.02). By use of a multiple
regression analysis, addition of the intensity of iNOS mRNA
expression as an independent variable significantly
(P<.005) improved the correlation between 
LVEST and
LV dP/dtmax (P<.001;
r=.97), implying a larger abbreviation of LV contraction
for a similar rise in LV dP/dtmax, when myocardial iNOS
mRNA was higher. The larger abbreviation of LV contraction in-patients
with high iNOS mRNA was associated with a decrease in LV
end-systolic pressure (-31±16 mm Hg).
Conclusions Myocardial iNOS gene expression in the human allograft influences the LV contractile response to ß-adrenergic stimulation through earlier onset of LV relaxation and reduction of LV end-systolic pressure. These effects are similar to the LV contractile effects of NO derived from NO donor or from coronary endothelium.
Key Words: transplantation • receptors, adrenergic, beta • endothelium-derived factors • myocardial contraction
This article has been cited by other articles:
 |
|
 |
|
  S. C. Stoica, D. K. Satchithananda, C. Atkinson, S. Charman, M. Goddard, and S. R. Large Heat shock protein, inducible nitric oxide synthase and apoptotic markers in the acute phase of human cardiac transplantation Eur. J. Cardiothorac. Surg., December 1, 2003; 24(6): 932 - 939. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Godecke, A. Molojavyi, J. Heger, U. Flogel, Z. Ding, C. Jacoby, and J. Schrader Myoglobin Protects the Heart from Inducible Nitric-oxide Synthase (iNOS)-mediated Nitrosative Stress J. Biol. Chem., June 6, 2003; 278(24): 21761 - 21766. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. L. Brutsaert Cardiac Endothelial-Myocardial Signaling: Its Role in Cardiac Growth, Contractile Performance, and Rhythmicity Physiol Rev, January 1, 2003; 83(1): 59 - 115. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Dai, P. S. Brookes, V. M. Darley-Usmar, and P. G. Anderson Bioenergetics in cardiac hypertrophy: mitochondrial respiration as a pathological target of NO{middle dot} Am J Physiol Heart Circ Physiol, December 1, 2001; 281(6): H2261 - H2269. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Cotton, M. T. Kearney, P. A. MacCarthy, R. M. Grocott-Mason, D. R. McClean, C. Heymes, P. J. Richardson, and A. M. Shah Effects of Nitric Oxide Synthase Inhibition on Basal Function and the Force-Frequency Relationship in the Normal and Failing Human Heart In Vivo Circulation, November 6, 2001; 104(19): 2318 - 2323. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Qian, R. Gelzer-Bell, S.-x. Yang, W. Cao, T. Ohnishi, B. A. Wasowska, R. H. Hruban, E. R. Rodriguez, W. M. Baldwin III, and C. J. Lowenstein Inducible Nitric Oxide Synthase Inhibition of Weibel-Palade Body Release in Cardiac Transplant Rejection Circulation, November 6, 2001; 104(19): 2369 - 2375. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D.L. Brutsaert Diagnosing primary diastolic heart failure Eur. Heart J., January 2, 2000; 21(2): 94 - 96. [PDF]
|
|
|
|
 |
|
 W. J Paulus and A. M Shah NO and cardiac diastolic function Cardiovasc Res, August 15, 1999; 43(3): 595 - 606. [Full Text] [PDF]
|
|
|
|
|
|
C. Heymes, M. Vanderheyden, J. G. F. Bronzwaer, A. M. Shah, and W. J. Paulus Endomyocardial Nitric Oxide Synthase and Left Ventricular Preload Reserve in Dilated Cardiomyopathy Circulation, June 15, 1999; 99(23): 3009 - 3016. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Kojda and K. Kottenberg Regulation of basal myocardial function by NO Cardiovasc Res, March 1, 1999; 41(3): 514 - 523. [Full Text] [PDF]
|
|
|
|
|
|
P. J. Cannon, X. Yang, M. J. Szabolcs, S. Ravalli, R. R. Sciacca, and R. E. Michler The role of inducible nitric oxide synthase in cardiac allograft rejection Cardiovasc Res, April 1, 1998; 38(1): 6 - 15. [Full Text] [PDF]
|
|
|
|
 |
|
 J. Heger, A. Godecke, U. Flogel, M. W. Merx, A. Molojavyi, W. N. Kuhn-Velten, and J. Schrader Cardiac-Specific Overexpression of Inducible Nitric Oxide Synthase Does Not Result in Severe Cardiac Dysfunction Circ. Res., January 11, 2002; 90(1): 93 - 99. [Abstract] [Full Text] [PDF]
|
|