(Circulation. 1996;93:1223-1229.)
© 1996 American Heart Association, Inc.
Articles |
Myocardial Contractile Response to Nitric Oxide and cGMP
From the Department of Physiology and Medicine, University of Antwerp, and the Cardiovascular Center (W.J.P.), O.L.V. Ziekenhuis, Aalst, Belgium.
Correspondence to Stanislas U. Sys, MD, PhD, Department of Physiology and Medicine, University of Antwerp (RUCA), Groenenborgerlaan 171, B-2020 Antwerp, Belgium.
Background Cardiac endothelium releases a number of factors that may modulate performance of underlying cardiac muscle. Nitric oxide (NO), which accounts for the biological activity of the vascular endothelium-derived relaxing factor and relaxes vascular smooth muscle by elevating intracellular cGMP, may be involved in this cardiac modulation.
Methods and Results We examined the myocardial contractile effects of the NO-releasing nitrovasodilators sodium nitroprusside (SNP), 3-morpholino-sydnonimine (SIN-1), and S-nitroso-N-acetyl-penicillamine (SNAP); of a cGMP analogue, 8-bromo-cGMP; and of the cGMP-phosphodiesterase inhibitor zaprinast in isolated cat papillary muscle. Modulation of these effects by endocardial endothelium (EE) and by cholinergic and adrenergic stimulation was also investigated. Concentration-response curves with addition of NO-releasing nitrovasodilators (SNP, SIN-1, SNAP) and 8-bromo-cGMP resulted in a biphasic inotropic response. Although administration of low concentrations induced a positive inotropic effect, higher concentrations induced a negative inotropic effect. Both NO-induced positive and negative inotropic effects were attenuated by methylene blue, suggesting a role for cGMP. The response to high concentrations of 8-bromo-cGMP was shifted to the right in muscles with damaged EE, whereas cholinergic stimulation shifted the curve leftward. Zaprinast caused a monophasic concentration-dependent positive inotropic effect; damaging the EE shifted the terminal portion of the curve upward. Concomitant cholinergic or adrenergic stimulation modified the response to zaprinast into a negative inotropic response.
Conclusions NO and cGMP induced a concentration-dependent biphasic contractile response. The myocardial contractile effects of NO and cGMP were modulated by the status of EE and by concomitant cholinergic or adrenergic stimulation.
Key Words: nitric oxide • myocardium • contractility • endothelium • endocardium
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]
|
|
|
|
 |
|
 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]
|
|
|
|
 |
|
 Z.-S. Zhang, H.-J. Cheng, K. Onishi, N. Ohte, T. Wannenburg, and C.-P. Cheng Enhanced Inhibition of L-type Ca2+ Current by {beta}3-Adrenergic Stimulation in Failing Rat Heart J. Pharmacol. Exp. Ther., December 1, 2005; 315(3): 1203 - 1211. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. D. Patten, D. DeNofrio, M. El-Zaru, R. Kakkar, J. Saunders, F. Celestin, K. Warner, H. Rastegar, K. R. Khabbaz, J. E. Udelson, et al. Ventricular Assist Device Therapy Normalizes Inducible Nitric Oxide Synthase Expression and Reduces Cardiomyocyte Apoptosis in the Failing Human Heart J. Am. Coll. Cardiol., May 3, 2005; 45(9): 1419 - 1424. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Ross, P. Engel, Y. Abdallah, W. Kummer, and K. D. Schluter Tuberoinfundibular Peptide of 39 Residues: A New Mediator of Cardiac Function via Nitric Oxide Production in the Rat Heart Endocrinology, May 1, 2005; 146(5): 2221 - 2228. [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]
|
|
|
|
|
|
W. J. Paulus and J. G. F. Bronzwaer Nitric oxide's role in the heart: control of beating or breathing? Am J Physiol Heart Circ Physiol, July 1, 2004; 287(1): H8 - H13. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. S. Farrar and K. J. Rodnick Sex-dependent effects of gonadal steroids and cortisol on cardiac contractility in rainbow trout J. Exp. Biol., May 15, 2004; 207(12): 2083 - 2093. [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. P. A. Mammen, S. B. Kanatous, I. S. Yuhanna, P. W. Shaul, M. G. Garry, R. S. Balaban, and D. J. Garry Hypoxia-induced left ventricular dysfunction in myoglobin-deficient mice Am J Physiol Heart Circ Physiol, November 1, 2003; 285(5): H2132 - H2141. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Cotter, E. Kaluski, O. Milo, A. Blatt, A. Salah, A. Hendler, R. Krakover, A. Golick, and Z. Vered LINCS: L-NAME (a NO synthase inhibitor) In the treatment of refractory Cardiogenic Shock: A prospective randomized study Eur. Heart J., July 2, 2003; 24(14): 1287 - 1295. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. A. Khan, M. W. Skaf, R. W. Harrison, K. Lee, K. M. Minhas, A. Kumar, M. Fradley, A. A. Shoukas, D. E. Berkowitz, and J. M. Hare Nitric Oxide Regulation of Myocardial Contractility and Calcium Cycling: Independent Impact of Neuronal and Endothelial Nitric Oxide Synthases Circ. Res., June 27, 2003; 92(12): 1322 - 1329. [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 M Cotton, M T Kearney, and A M Shah Nitric oxide and myocardial function in heart failure: friend or foe? Heart, December 1, 2002; 88(6): 564 - 566. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Saito, F. Hu, L. Tayara, L. Fahas, H. Shennib, and A. Giaid Inhibition of NOS II prevents cardiac dysfunction in myocardial infarction and congestive heart failure Am J Physiol Heart Circ Physiol, July 1, 2002; 283(1): H339 - H345. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E Belcher, J Mitchell, and T Evans Myocardial dysfunction in sepsis: no role for NO? Heart, June 1, 2002; 87(6): 507 - 509. [Full Text] [PDF]
|
|
|
|
 |
|
 J. G. Lainchbury, O. Lisy, J. C. Burnett Jr., D. M. Meyer, and M. M. Redfield Actions of a novel synthetic natriuretic peptide on hemodynamics and ventricular function in the dog Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2002; 282(4): R993 - R998. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Stangl, G. Baumann, K. Stangl, and S. B Felix Negative inotropic mediators released from the heart after myocardial ischaemia-reperfusion Cardiovasc Res, January 1, 2002; 53(1): 12 - 30. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. A. Nikolaidis, T. Hentosz, A. Doverspike, R. Huerbin, C. Stolarski, Y.-T. Shen, and R. P. Shannon Mechanisms whereby rapid RV pacing causes LV dysfunction: perfusion-contraction matching and NO Am J Physiol Heart Circ Physiol, December 1, 2001; 281(6): H2270 - H2281. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. J. Paulus, S. Frantz, and R. A. Kelly Nitric Oxide and Cardiac Contractility in Human Heart Failure: Time for Reappraisal Circulation, November 6, 2001; 104(19): 2260 - 2262. [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]
|
|
|
|
|
|
S. C. Tjen-A-Looi, N. T. Phan, and J. C. Longhurst Nitric oxide modulates sympathoexcitatory cardiac-cardiovascular reflexes elicited by bradykinin Am J Physiol Heart Circ Physiol, November 1, 2001; 281(5): H2010 - H2017. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. D. Monti, S. Allibardi, P. M. Piatti, G. Valsecchi, S. Costa, G. Pozza, S. Chierchia, and M. Samaja Triglycerides impair postischemic recovery in isolated hearts: roles of endothelin-1 and trimetazidine Am J Physiol Heart Circ Physiol, September 1, 2001; 281(3): H1122 - H1130. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. SENZAKI, C. J. SMITH1, G. J. JUANG, T. ISODA, S. P. MAYER, A. OHLER, N. PAOLOCCI, G. F. TOMASELLI, J. M. HARE, and D. A. KASS Cardiac phosphodiesterase 5 (cGMP-specific) modulates {beta}-adrenergic signaling in vivo and is down-regulated in heart failure FASEB J, August 1, 2001; 15(10): 1718 - 1726. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. O. Stojanovic, M. T. Ziolo, G. M. Wahler, and B. M. Wolska Anti-adrenergic effects of nitric oxide donor SIN-1 in rat cardiac myocytes Am J Physiol Cell Physiol, July 1, 2001; 281(1): C342 - C349. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Stumpe, U. K. M. Decking, and J. Schrader Nitric oxide reduces energy supply by direct action on the respiratory chain in isolated cardiomyocytes Am J Physiol Heart Circ Physiol, May 1, 2001; 280(5): H2350 - H2356. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. D. Lasley, M. S. Jahania, and R. M. Mentzer Jr. Beneficial effects of adenosine A2a agonist CGS-21680 in infarcted and stunned porcine myocardium Am J Physiol Heart Circ Physiol, April 1, 2001; 280(4): H1660 - H1666. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. J. Zieman, G. Gerstenblith, E. G. Lakatta, G. O. Rosas, K. Vandegaer, K. M. Ricker, and J. M. Hare Upregulation of the Nitric Oxide-cGMP Pathway in Aged Myocardium : Physiological Response to l-Arginine Circ. Res., January 19, 2001; 88(1): 97 - 102. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Paolocci, U. E. G. Ekelund, T. Isoda, M. Ozaki, K. Vandegaer, D. Georgakopoulos, R. W. Harrison, D. A. Kass, and J. M. Hare cGMP-independent inotropic effects of nitric oxide and peroxynitrite donors: potential role for nitrosylation Am J Physiol Heart Circ Physiol, October 1, 2000; 279(4): H1982 - H1988. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Thuringer, C. Rucker-Martin, and C. Frelin Cardiac capillary cells release biologically active nitric oxide at an early stage of in vitro development Cardiovasc Res, September 1, 2000; 47(4): 726 - 737. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Sata, M. Kakoki, D. Nagata, H. Nishimatsu, E. Suzuki, T. Aoyagi, S. Sugiura, H. Kojima, T. Nagano, K. Kangawa, et al. Adrenomedullin and Nitric Oxide Inhibit Human Endothelial Cell Apoptosis via a Cyclic GMP-Independent Mechanism Hypertension, July 1, 2000; 36(1): 83 - 88. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Gyurko, P. Kuhlencordt, M. C. Fishman, and P. L. Huang Modulation of mouse cardiac function in vivo by eNOS and ANP Am J Physiol Heart Circ Physiol, March 1, 2000; 278(3): H971 - H981. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. G. Lainchbury, J. C. Burnett Jr., D. Meyer, and M. M. Redfield Effects of natriuretic peptides on load and myocardial function in normal and heart failure dogs Am J Physiol Heart Circ Physiol, January 1, 2000; 278(1): H33 - H40. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. J. Lee, S. Z. Kim, X. Cui, S. H. Kim, K. S. Lee, Y. J. Chung, and K. W. Cho C-type natriuretic peptide inhibits ANP secretion and atrial dynamics in perfused atria: NPR-B-cGMP signaling Am J Physiol Heart Circ Physiol, January 1, 2000; 278(1): H208 - H221. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. R. Murray, S. D. Prabhu, and G. L. Freeman Hemodynamic effects of nitric oxide synthase inhibition at steady state and following tumor necrosis factor-{alpha}-induced myodepression Cardiovasc Res, December 1, 1999; 44(3): 527 - 535. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Yang, D. F. Larson, and R. Watson Age-related left ventricular function in the mouse: analysis based on in vivo pressure-volume relationships Am J Physiol Heart Circ Physiol, November 1, 1999; 277(5): H1906 - H1913. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. V. Brahmajothi and D. L. Campbell Heterogeneous Basal Expression of Nitric Oxide Synthase and Superoxide Dismutase Isoforms in Mammalian Heart : Implications for Mechanisms Governing Indirect and Direct Nitric Oxide-Related Effects Circ. Res., October 1, 1999; 85(7): 575 - 587. [Abstract] [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]
|
|
|
|
|
|
C. S Hayward, R. P Kelly, and P. S Macdonald Inhaled nitric oxide in cardiology practice Cardiovasc Res, August 15, 1999; 43(3): 628 - 638. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Masciotra, S. Picard, and C. F. Deschepper Cosegregation Analysis in Genetic Crosses Suggests a Protective Role for Atrial Natriuretic Factor Against Ventricular Hypertrophy Circ. Res., June 25, 1999; 84(12): 1453 - 1458. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Drexler Nitric Oxide Synthases in the Failing Human Heart : A Doubled-Edged Sword? Circulation, June 15, 1999; 99(23): 2972 - 2975. [Full Text] [PDF]
|
|
|
|
|
|
M. G. Vila-Petroff, A. Younes, J. Egan, E. G. Lakatta, and S. J. Sollott Activation of Distinct cAMP-Dependent and cGMP-Dependent Pathways by Nitric Oxide in Cardiac Myocytes Circ. Res., May 14, 1999; 84(9): 1020 - 1031. [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]
|
|
|
|
|
|
G. Alloatti, C. Penna, A. De Martino, G. Montrucchio, and G. Camussi Role of nitric oxide and platelet-activating factor in cardiac alterations induced by tumor necrosis factor-{alpha} in the guinea-pig papillary muscle Cardiovasc Res, March 1, 1999; 41(3): 611 - 619. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. J. Ing, J. Zang, V. J. Dzau, K. A. Webster, and N. H. Bishopric Modulation of Cytokine-Induced Cardiac Myocyte Apoptosis by Nitric Oxide, Bak, and Bcl-x Circ. Res., January 22, 1999; 84(1): 21 - 33. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. A. Recchia, P. I. McConnell, R. D. Bernstein, T. R. Vogel, X. Xu, and T. H. Hintze Reduced Nitric Oxide Production and Altered Myocardial Metabolism During the Decompensation of Pacing-Induced Heart Failure in the Conscious Dog Circ. Res., November 16, 1998; 83(10): 969 - 979. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Stein, T. Eschenhagen, J. Rudiger, H. Scholz, U. Forstermann, and I. Gath Increased expression of constitutive nitric oxide synthase III, but not inducible nitric oxide synthase II, in human heart failure J. Am. Coll. Cardiol., November 1, 1998; 32(5): 1179 - 1186. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Bartunek, S. Dempsey, E. O. Weinberg, N. Ito, M. Tajima, S. Rohrbach, and B. H. Lorell Chronic L-arginine treatment increases cardiac cyclic guanosine 5'-monophosphate in rats with aortic stenosis: effects on left ventricular mass and beta-adrenergic contractile reserve J. Am. Coll. Cardiol., August 1, 1998; 32(2): 528 - 535. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Suto, A. Mikuniya, T. Okubo, H. Hanada, N. Shinozaki, and K. Okumura Nitric oxide modulates cardiac contractility and oxygen consumption without changing contractile efficiency Am J Physiol Heart Circ Physiol, July 1, 1998; 275(1): H41 - H49. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. U Sys, G. W De Keulenaer, and D. L Brutsaert Physiopharmacological evaluation of myocardial performance: how to study modulation by cardiac endothelium and related humoral factors? Cardiovasc Res, July 1, 1998; 39(1): 136 - 147. [Full Text] [PDF]
|
|
|
|
 |
|
 I. S. Ali, M. Gandhi, B. A. Finegan, A. Koshal, and A. S. Clanachan Cardioprotection by Activation of NO/cGMP Pathway After Cardioplegic Arrest and 8-Hour Storage Ann. Thorac. Surg., May 1, 1998; 65(5): 1303 - 1309. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. L. Brutsaert, P. Fransen, L. J. Andries, G. W. De Keulenaer, and S. U. Sys Cardiac endothelium and myocardial function Cardiovasc Res, May 1, 1998; 38(2): 281 - 290. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. A De Mulder, S. G De Hert, R. J Van Kerckhoven, H. F Adriaensen, and T. C Gillebert Sodium nitroprusside enhances in vivo left ventricular function in {beta}-adrenergically stimulated rabbit hearts Cardiovasc Res, April 1, 1998; 38(1): 133 - 139. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. E Klabunde, J. Tse, and H. R Weiss Guanylyl cyclase inhibition reduces contractility and decreases cGMP and cAMP in isolated rat hearts Cardiovasc Res, March 1, 1998; 37(3): 676 - 683. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. J. Andries, D. L. Brutsaert, and S. U. Sys Nonuniformity of Endothelial Constitutive Nitric Oxide Synthase Distribution in Cardiac Endothelium Circ. Res., February 9, 1998; 82(2): 195 - 203. [Abstract] [Full Text] [PDF]
|
|
|
|