Articles |
From the Department of Medicine (D.J.P.), Columbia University College of Physicians and Surgeons, New York, NY, and the Department of Chemistry and Institute of Biotechnology (D.J.P., S.P., S.M., V.B., E.K., S.G., T.M.), Oakland University, Rochester, Michigan.
Correspondence to Dr Tadeusz Malinski/Dr David J. Pinsky, Oakland University, Department of Chemistry and Institute of Biotechnology, Rochester, MI 48309-4401.
Abstract NO alters contractile and relaxant properties of the heart. However, it is not known whether changes in ventricular loading conditions affect cardiac NO synthesis. To understand this potential contractile-relaxant autoregulatory mechanism, production of cardiac NO in response to mechanical stimuli was measured in vivo using a porphyrinic sensor placed in the left ventricular myocardium. The beating rabbit heart exhibited cyclic changes in [NO], peaking at 2.7±0.1 µmol/L near the endocardium and 0.93±0.20 µmol/L in the midventricular myocardium (concentrations were 15±4% lower in the rat heart). In the present study, we demonstrate for the first time that increasing or decreasing ventricular preload in vivo is followed by parallel changes in [NO], which may represent a novel autoregulatory mechanism to adjust cardiac performance or perfusion on a beat-to-beat basis. To quantify the relationship between applied force and NO synthesis, intermittent compressive or distending forces applied to ex vivo nonbeating hearts were shown to cause bursts of NO synthesis, with peak [NO] linearly related to ventricular transmural pressure. Experiments in which denuding cardiac endothelial and endocardial cells abrogated the NO signal indicate that these cells transduce mechanical stimulation into NO production in the heart. Taken together, these studies may help explain load-dependent relaxation, cardiac memory for mechanical events of preceding beats, diseases associated with myocardial distension, autoregulation of myocardial perfusion, and protection from thrombosis in the turbulent flow environment within the beating heart.
Key Words: left ventricular myocardium mechanical stimulus porphyrinic sensor rabbit rat
This article has been cited by other articles:
![]() |
F. Garofalo, M. L. Parisella, D. Amelio, B. Tota, and S. Imbrogno Phospholamban S-nitrosylation modulates Starling response in fish heart Proc R Soc B, November 22, 2009; 276(1675): 4043 - 4052. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. E. Brack, V. H. Patel, R. Mantravardi, J. H. Coote, and G. A. Ng Direct evidence of nitric oxide release from neuronal nitric oxide synthase activation in the left ventricle as a result of cervical vagus nerve stimulation J. Physiol., June 15, 2009; 587(12): 3045 - 3054. [Abstract] [Full Text] [PDF] |
||||
![]() |
J.-L. Balligand, O. Feron, and C. Dessy eNOS Activation by Physical Forces: From Short-Term Regulation of Contraction to Chronic Remodeling of Cardiovascular Tissues Physiol Rev, April 1, 2009; 89(2): 481 - 534. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. von Lewinski, J. Kockskamper, D. Zhu, H. Post, A. Elgner, and B. Pieske Reduced Stretch-Induced Force Response in Failing Human Myocardium Caused by Impaired Na+-Contraction Coupling Circ Heart Fail, January 1, 2009; 2(1): 47 - 55. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. G.F. Bronzwaer and W. J. Paulus Nitric oxide: the missing lusitrope in failing myocardium Eur. Heart J., October 2, 2008; 29(20): 2453 - 2455. [Full Text] [PDF] |
||||
![]() |
P. La Padula, J. Bustamante, A. Czerniczyniec, and L. E. Costa Time course of regression of the protection conferred by simulated high altitude to rat myocardium: correlation with mtNOS J Appl Physiol, September 1, 2008; 105(3): 951 - 957. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Hallstrom, M. Franz, H. Gasser, M. Vodrazka, S. Semsroth, U. M. Losert, M. Haisjackl, B. K. Podesser, and T. Malinski S-nitroso human serum albumin reduces ischaemia/reperfusion injury in the pig heart after unprotected warm ischaemia Cardiovasc Res, February 1, 2008; 77(3): 506 - 514. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. Lim, L. Venetucci, D. A. Eisner, and B. Casadei Does nitric oxide modulate cardiac ryanodine receptor function? Implications for excitation-contraction coupling Cardiovasc Res, January 15, 2008; 77(2): 256 - 264. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Seddon, A. M. Shah, and B. Casadei Cardiomyocytes as effectors of nitric oxide signalling Cardiovasc Res, July 15, 2007; 75(2): 315 - 326. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. H. Tran, P. Andreka, C. O. Rodrigues, K. A. Webster, and N. H. Bishopric Jun Kinase Delays Caspase-9 Activation by Interaction with the Apoptosome J. Biol. Chem., July 13, 2007; 282(28): 20340 - 20350. [Abstract] [Full Text] [PDF] |
||||
![]() |
E. N. Dedkova, Y. G. Wang, X. Ji, L. A. Blatter, A. M. Samarel, and S. L. Lipsius Signalling mechanisms in contraction-mediated stimulation of intracellular NO production in cat ventricular myocytes J. Physiol., April 1, 2007; 580(1): 327 - 345. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. Imanishi, K. Kobayashi, A. Kuroi, S. Mochizuki, M. Goto, K. Yoshida, and T. Akasaka Effects of Angiotensin II on NO Bioavailability Evaluated Using a Catheter-Type NO Sensor Hypertension, December 1, 2006; 48(6): 1058 - 1065. [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] |
||||
![]() |
M. A. Sackner, E. Gummels, and J. A. Adams Effect of Moderate-Intensity Exercise, Whole-Body Periodic Acceleration, and Passive Cycling on Nitric Oxide Release Into Circulation Chest, October 1, 2005; 128(4): 2794 - 2803. [Abstract] [Full Text] [PDF] |
||||
![]() |
Y. Neishi, S. Mochizuki, T. Miyasaka, T. Kawamoto, T. Kume, R. Sukmawan, M. Tsukiji, Y. Ogasawara, F. Kajiya, T. Akasaka, et al. Evaluation of bioavailability of nitric oxide in coronary circulation by direct measurement of plasma nitric oxide concentration PNAS, August 9, 2005; 102(32): 11456 - 11461. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. Zaobornyj, L. B. Valdez, P. La Padula, L. E. Costa, and A. Boveris Effect of sustained hypobaric hypoxia during maturation and aging on rat myocardium. II. mtNOS activity J Appl Physiol, June 1, 2005; 98(6): 2370 - 2375. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. C. Tyagi, W. Rodriguez, A. M. Patel, A. M. Roberts, J. C. Falcone, J. C. Passmore, J. T. Fleming, and I. G. Joshua Hyperhomocysteinemic Diabetic Cardiomyopathy: Oxidative Stress, Remodeling, and Endothelial-Myocyte Uncoupling Journal of Cardiovascular Pharmacology and Therapeutics, January 1, 2005; 10(1): 1 - 10. [Abstract] [PDF] |
||||
![]() |
M. A. Sackner, E. Gummels, and J. A. Adams Nitric Oxide Is Released Into Circulation With Whole-Body, Periodic Acceleration Chest, January 1, 2005; 127(1): 30 - 39. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. Sun, A. Huang, and G. Kaley Mechanical compression elicits NO-dependent increases in coronary flow Am J Physiol Heart Circ Physiol, December 1, 2004; 287(6): H2454 - H2460. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. Pellegrino, C. A. Palmerini, and B. Tota No hemoglobin but NO: the icefish (Chionodraco hamatus) heart as a paradigm J. Exp. Biol., October 15, 2004; 207(22): 3855 - 3864. [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] |
||||
![]() |
J. White, D. L. Carlson, M. Thompson, D. L. Maass, B. Sanders, B. Giroir, and J. W. Horton Molecular and pharmacological approaches to inhibiting nitric oxide after burn trauma Am J Physiol Heart Circ Physiol, October 1, 2003; 285(4): H1616 - H1625. [Abstract] [Full Text] [PDF] |
||||
![]() |
W. Linz, G. Itter, L. W Dobrucki, T. Malinski, and G. Wiemer Ramipril improves nitric oxide availability in hypertensive rats with failing hearts after myocardial infarction Journal of Renin-Angiotensin-Aldosterone System, September 1, 2003; 4(3): 180 - 185. [Abstract] [PDF] |
||||
![]() |
A. W. Cohen, D. S. Park, S. E. Woodman, T. M. Williams, M. Chandra, J. Shirani, A. Pereira de Souza, R. N. Kitsis, R. G. Russell, L. M. Weiss, et al. Caveolin-1 null mice develop cardiac hypertrophy with hyperactivation of p42/44 MAP kinase in cardiac fibroblasts Am J Physiol Cell Physiol, February 1, 2003; 284(2): C457 - C474. [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. G. F. Bronzwaer, C. Heymes, C. A. Visser, and W. J. Paulus Myocardial fibrosis blunts nitric oxide synthase-related preload reserve in human dilated cardiomyopathy Am J Physiol Heart Circ Physiol, January 1, 2003; 284(1): H10 - H16. [Abstract] [Full Text] [PDF] |
||||
![]() |
Y. Higashi, K. Nakagawa, M. Kimura, K. Noma, K. Hara, S. Sasaki, C. Goto, T. Oshima, K. Chayama, and M. Yoshizumi Circadian variation of blood pressure and endothelial function in patients with essential hypertension: a comparison of dippers and non-dippers J. Am. Coll. Cardiol., December 4, 2002; 40(11): 2039 - 2043. [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] |
||||
![]() |
A. N. Friedman, C. Ritter, J. C. F. Moreira, F. Dal-Pizzol, M. G. Ziegler, X. Bao, R. Matz, Y. Higashi, K. Chayama, and M. Yoshizumi Renovascular Hypertension, Endothelial Function, and Oxidative Stress N. Engl. J. Med., November 7, 2002; 347(19): 1528 - 1530. [Full Text] [PDF] |
||||
![]() |
B. K. Podesser, J. Schirnhofer, O. Y. Bernecker, A. Kroner, M. Franz, S. Semsroth, B. Fellner, J. Neumuller, S. Hallstrom, and E. Wolner Optimizing Ischemia/Reperfusion in the Failing Rat Heart--Improved Myocardial Protection With Acute ACE Inhibition Circulation, September 24, 2002; 106(12_suppl_1): I-277 - I-283. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. J. Hunt, G. M. Aru, M. R. Hayden, C. K. Moore, B. D. Hoit, and S. C. Tyagi Induction of oxidative stress and disintegrin metalloproteinase in human heart end-stage failure Am J Physiol Lung Cell Mol Physiol, August 1, 2002; 283(2): L239 - L245. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. L. Jackman, M. G. Massad, M. Sekosan, F. Tan, V. Brovkovych, B. M. Marcic, and E. G. Erdos Angiotensin 1-9 and 1-7 Release in Human Heart: Role of Cathepsin A Hypertension, May 1, 2002; 39(5): 976 - 981. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. Sarkar, P. Vallance, and S. E. Harding Nitric oxide: not just a negative inotrope Eur J Heart Fail, October 1, 2001; 3(5): 527 - 534. [Abstract] [Full Text] [PDF] |
||||
![]() |
V. Brovkovych, L. W. Dobrucki, S. Brovkovych, I. Dobrucki, L. Kalinowski, F. Kiechle, and T. Malinski Nitric Oxide Measurements during Endotoxemia Clin. Chem., June 1, 2001; 47(6): 1068 - 1074. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. D. Rakhit, M. H. Mojet, M. S. Marber, and M. R. Duchen Mitochondria as Targets for Nitric Oxide-Induced Protection During Simulated Ischemia and Reoxygenation in Isolated Neonatal Cardiomyocytes Circulation, May 29, 2001; 103(21): 2617 - 2623. [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] |
||||
![]() |
J. S. Stamler and G. Meissner Physiology of Nitric Oxide in Skeletal Muscle Physiol Rev, January 1, 2001; 81(1): 209 - 237. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. B. Zorov, C. R. Filburn, L.-O. Klotz, J. L. Zweier, and S. J. Sollott Reactive Oxygen Species (Ros-Induced) Ros Release: A New Phenomenon Accompanying Induction of the Mitochondrial Permeability Transition in Cardiac Myocytes J. Exp. Med., October 2, 2000; 192(7): 1001 - 1014. [Abstract] [Full Text] [PDF] |
||||
![]() |
F. A. Recchia, T. R. Vogel, and T. H. Hintze NO metabolites accumulate in erythrocytes in proportion to carbon dioxide and bicarbonate concentration Am J Physiol Heart Circ Physiol, August 1, 2000; 279(2): H852 - H856. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. F. Soto, C.-X. Jia, D. G. Rabkin, J. P. Hart, Y. M. Carter, M. J. Sardo, D. T. Hsu, P. E. Fisher, D. J. Pinsky, and H. M. Spotnitz Improvement of rejection-induced diastolic abnormalities in rat cardiac allografts with inducible nitric oxide synthase inhibition J. Thorac. Cardiovasc. Surg., July 1, 2000; 120(1): 39 - 46. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. Y. Wang, I. Aronson, S. Takuma, S. Homma, Y. Naka, T. Alshafie, V. Brovkovych, T. Malinski, M. C. Oz, and D. J. Pinsky cAMP Pulse During Preservation Inhibits the Late Development of Cardiac Isograft and Allograft Vasculopathy Circ. Res., May 12, 2000; 86(9): 982 - 988. [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] |
||||
![]() |
D. J. Pinsky, W. Aji, M. Szabolcs, E. S. Athan, Y. Liu, Y. M. Yang, R. P. Kline, K. E. Olson, and P. J. Cannon Nitric oxide triggers programmed cell death (apoptosis) of adult rat ventricular myocytes in culture Am J Physiol Heart Circ Physiol, September 1, 1999; 277(3): H1189 - H1199. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. S. Gross and P. Lane Physiological reactions of nitric oxide and hemoglobin: A radical rethink PNAS, August 31, 1999; 96(18): 9967 - 9969. [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] |
||||
![]() |
P. Musialek, D. J Paterson, and B. Casadei Changes in extracellular pH mediate the chronotropic responses to L-arginine Cardiovasc Res, August 15, 1999; 43(3): 712 - 720. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. J. Gow, B. P. Luchsinger, J. R. Pawloski, D. J. Singel, and J. S. Stamler The oxyhemoglobin reaction of nitric oxide PNAS, August 3, 1999; 96(16): 9027 - 9032. [Abstract] [Full Text] [PDF] |
||||
![]() |
W. Linz, P. Wohlfart, B. A. Schoelkens, R. H. A. Becker, T. Malinski, and G. Wiemer Late Treatment With Ramipril Increases Survival in Old Spontaneously Hypertensive Rats Hypertension, August 1, 1999; 34(2): 291 - 295. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. Merkus, F. Kajiya, H. Vink, I. Vergroesen, J. Dankelman, M. Goto, and J. A. E. Spaan Prolonged Diastolic Time Fraction Protects Myocardial Perfusion When Coronary Blood Flow Is Reduced Circulation, July 6, 1999; 100(1): 75 - 81. [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] |
||||
![]() |
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] |
||||
![]() |
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] |
||||
![]() |
E. Toyota, M. Goto, H. Nakamoto, J. Ebata, H. Tachibana, O. Hiramatsu, Y. Ogasawara, and F. Kajiya Endothelium-derived nitric oxide enhances the effect of intraaortic balloon pumping on diastolic coronary flow Ann. Thorac. Surg., May 1, 1999; 67(5): 1254 - 1261. [Abstract] [Full Text] [PDF] |
||||
![]() |
A Escrig, J L Gonzalez-Mora, and M Mas Nitric oxide release in penile corpora cavernosa in a rat model of erection J. Physiol., April 1, 1999; 516(1): 261 - 269. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. R. Rosen, I. S. Cohen, P. Danilo Jr., and S. F. Steinberg The heart remembers Cardiovasc Res, December 1, 1998; 40(3): 469 - 482. [Full Text] [PDF] |
||||
![]() |
A. M Shah, S. J Sollott, and E. G Lakatta Physio-pharmacological evaluation of myocardial performance: an integrative approach Cardiovasc Res, July 1, 1998; 39(1): 148 - 154. [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] |
||||
![]() |
J.-L. Balligand and P. J. Cannon Nitric Oxide Synthases and Cardiac Muscle : Autocrine and Paracrine Influences Arterioscler Thromb Vasc Biol, October 1, 1997; 17(10): 1846 - 1858. [Abstract] [Full Text] |
||||
|
Circulation Research Home | Subscriptions | Archives | Feedback | Authors | Help | AHA Journals Home | Search Copyright © 1997 American Heart Association, Inc. All rights reserved. Unauthorized use prohibited. |