![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Vol. 281, Issue 3, 1340-1349, 1997
Klinik III für Innere Medizin and Klinik für
Herzchirurgie (M.S., F.K.-R.) der Universität zu Köln,
50924 Köln, Germany
Evidence that the activity of nitric oxide synthase and the generation
of nitric oxide (NO) within the myocardium are enhanced in several
cardiovascular disorders is increasing. Findings whether NO exerts a
direct effect on cardiac contractility are contradictory. Therefore,
the direct effect of the NO donor sodium nitroprusside (SNP) on
isometric force of contraction of human atrial and ventricular myocardium was investigated, and the question was addressed whether the
effects of NO on cardiac contractility are mediated via
cGMP. Experiments were performed on isolated electrically driven (1Hz, 37°C) human right atrial trabecula and left ventricular papillary muscle preparations from nonfailing and terminally failing hearts. SNP
led to a concentration-dependent decrease of force of contraction (FOC)
with a maximum effect at 100 µmol/l. In atrial trabecula, SNP (100 µmol/l) caused an acute decrease in basal FOC as well as in FOC after
application of isoprenaline or IBMX by 12.5 ± 5% (P < .05), 16.6 ± 3.7% (P < .05) and 18.3 ± 4.2% (P < .05), respectively. The negative inotropic effects could be
attenuated by the guanylyl cyclase inhibitor methylene blue. In
papillary muscle preparations, NO release caused a maximum decrease in
basal and in isoprenaline-enhanced FOC of 11.0 ± 1.9% (P < .05) and 23.6 ± 1.5% (P < .05), respectively. In the
presence of isoprenaline, the reduction of FOC was less pronounced in
failing than in nonfailing papillary muscles. 8-bromo-cGMP caused a
38.2 ± 5.2% decrease in atrial trabecula contractility. Both SNP
and 8-bromo-cGMP caused a shortening of the contractile twitch with a
premature onset of relaxation. As determined by radioimmunoassay,
exposure of atrial trabecula to SNP (100 µmol) led to a 6-fold
increase in myocardial cGMP concentrations, which could be attenuated
by methylene blue. In conclusion, NO exerts a negative inotropic effect
on human atrial and ventricular myocardium which seems to be mediated via generation of cGMP. The release of NO within the
myocardium in a variety of cardiovascular disorders might explain
decreases in cardiac contractility. The control of NO release could be
an important target for future therapeutical interventions in these pathological conditions.
This article has been cited by other articles:
|
|
 |
|
  S. J. Nicholls, Z. Wang, R. Koeth, B. Levison, B. DelFraino, V. Dzavik, O. W. Griffith, D. Hathaway, J. A. Panza, S. E. Nissen, et al. Metabolic Profiling of Arginine and Nitric Oxide Pathways Predicts Hemodynamic Abnormalities and Mortality in Patients With Cardiogenic Shock After Acute Myocardial Infarction Circulation, November 13, 2007; 116(20): 2315 - 2324. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. A. Kass, E. Takimoto, T. Nagayama, and H. C. Champion Phosphodiesterase regulation of nitric oxide signaling Cardiovasc Res, July 15, 2007; 75(2): 303 - 314. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Casadei The emerging role of neuronal nitric oxide synthase in the regulation of myocardial function Exp Physiol, November 1, 2006; 91(6): 943 - 955. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. D. Maslow, G. Stearns, P. Batula, C. S. Schwartz, J. Gough, and A. K. Singh The hemodynamic effects of methylene blue when administered at the onset of cardiopulmonary bypass. Anesth. Analg., July 1, 2006; 103(1): 2 - 8. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. S. Jung, H. Kubo, R. Wilson, S. R. Houser, and K. B. Margulies Modulation of contractility by myocyte-derived arginase in normal and hypertrophied feline myocardium Am J Physiol Heart Circ Physiol, May 1, 2006; 290(5): H1756 - H1762. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Ruetten, S. Dimmeler, D. Gehring, C. Ihling, and A. M. Zeiher Concentric left ventricular remodeling in endothelial nitric oxide synthase knockout mice by chronic pressure overload Cardiovasc Res, June 1, 2005; 66(3): 444 - 453. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. F. Leite-Moreira and C. Bras-Silva Inotropic effects of ETB receptor stimulation and their modulation by endocardial endothelium, NO, and prostaglandins Am J Physiol Heart Circ Physiol, September 1, 2004; 287(3): H1194 - H1199. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. von Lewinski, B. Stumme, F. Fialka, C. Luers, and B. Pieske Functional Relevance of the Stretch-Dependent Slow Force Response in Failing Human Myocardium Circ. Res., May 28, 2004; 94(10): 1392 - 1398. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. F. Wen, X. Cui, J. Y. Jin, S. M. Kim, S. Z. Kim, S. H. Kim, H. S. Lee, and K. W. Cho High and Low Gain Switches for Regulation of cAMP Efflux Concentration: Distinct Roles for Particulate GC- and Soluble GC-cGMP-PDE3 Signaling in Rabbit Atria Circ. Res., April 16, 2004; 94(7): 936 - 943. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Dazert, K. Meissner, S. Vogelgesang, B. Heydrich, L. Eckel, M. Bohm, R. Warzok, R. Kerb, U. Brinkmann, E. Schaeffeler, et al. Expression and Localization of the Multidrug Resistance Protein 5 (MRP5/ABCC5), a Cellular Export Pump for Cyclic Nucleotides, in Human Heart Am. J. Pathol., October 1, 2003; 163(4): 1567 - 1577. [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]
|
|
|
|
 |
|
 J.-B. Shen and A. J. Pappano On the Role of Phosphatase in Regulation of Cardiac L-Type Calcium Current by Cyclic GMP J. Pharmacol. Exp. Ther., May 1, 2002; 301(2): 501 - 506. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. T. Ziolo, H. Katoh, and D. M. Bers Expression of Inducible Nitric Oxide Synthase Depresses {beta}-Adrenergic-Stimulated Calcium Release From the Sarcoplasmic Reticulum in Intact Ventricular Myocytes Circulation, December 11, 2001; 104(24): 2961 - 2966. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Liu, D. Song, and S. S. Lee Role of heme oxygenase-carbon monoxide pathway in pathogenesis of cirrhotic cardiomyopathy in the rat Am J Physiol Gastrointest Liver Physiol, January 1, 2001; 280(1): G68 - G74. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O.-E. Brodde and M. C. Michel Adrenergic and Muscarinic Receptors in the Human Heart Pharmacol. Rev., December 1, 1999; 51(4): 651 - 690. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Krieg, T. Wahlers, W. Giess, R. Rohde, M. Hartrumpf, M. Bund, and A. Haverich Inhaled nitric oxide and inhaled prostaglandin E1: effect on left ventricular contractility when used for treatment of experimental pulmonary hypertension Eur. J. Cardiothorac. Surg., November 1, 1999; 14(5): 494 - 502. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Linz, P. Wohlfart, B. A Scholkens, T. Malinski, and G. Wiemer Interactions among ACE, kinins and NO Cardiovasc Res, August 15, 1999; 43(3): 549 - 561. [Full Text] [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]
|
|
|
|
|
|
J.-L. Balligand Regulation of cardiac {beta}-adrenergic response by nitric oxide Cardiovasc Res, August 15, 1999; 43(3): 607 - 620. [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]
|
|
|
|
|
|
S. E. Harding, C. H. Davies, A. M. Money-Kyrle, and P. A. Poole-Wilson An inhibitor of nitric oxide synthase does not increase contraction or {beta}-adrenoceptor sensitivity of ventricular myocytes from failing human heart Cardiovasc Res, December 1, 1998; 40(3): 523 - 529. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Layland, J.-M. Li, and A. M. Shah Role of cyclic GMP-dependent protein kinase in the contractile response to exogenous nitric oxide in rat cardiac myocytes J. Physiol., April 15, 2002; 540(2): 457 - 467. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
