HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 540/2/457    most recent 2001.014126v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Layland, J. Articles by Shah, A. M. Search for Related Content PubMed PubMed Citation Articles by Layland, J. Articles by Shah, A. M.

Role of cyclic GMP-dependent protein kinase in the contractile response to exogenous nitric oxide in rat cardiac myocytes

Joanne Layland, Jian-Mei Li and Ajay M. Shah

Nitric oxide (NO) can directly modulate cardiac contractility by accelerating relaxation and reducing diastolic tone. The intracellular mechanisms underlying these contractile effects are poorly understood. Here we investigate the role of cyclic GMP-dependent protein kinase (PKG) in the contractile response to exogenous NO in rat ventricular myocytes. Isolated ventricular myocytes were stimulated electrically and contractility was assessed by measuring cell shortening. Some cells were loaded with the fluorescent Ca²⁺ probe indo-1 AM for simultaneous assessment of the intracellular Ca²⁺ transient. The NO donor diethylamine NONOate (DEA/NO, 10 µM) significantly increased resting cell length, reduced twitch amplitude and accelerated time to 50 % relaxation (to 100.8 ± 0.2, 83.7 ± 3.0 and 88.9 ± 3.7 % of control values, respectively). The contractile effects of DEA/NO occurred without significant changes in the amplitude or kinetics of the intracellular Ca²⁺ transient, suggesting that the myofilament response to Ca²⁺ was reduced. These effects were abolished by inhibition of either guanylyl cyclase (with 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one; ODQ, 10 µM) or PKG (with Rp-8-Br-cGMPs, 10 µM) suggesting that, at the concentration investigated, the effects of DEA/NO were mediated exclusively by PKG, following activation of guanylyl cyclase and elevation of cGMP. Direct activation of PKG with 8-pCPT-cGMP (10 µM) mimicked the effects of DEA/NO (resting cell length and time to 50 % relaxation were 100.6 ± 0.1 and 90.5 ± 1.5 % of control values, respectively).The reduced myofilament Ca²⁺ responsiveness was not attributable to an intracellular acidosis since the small reduction in pH_i induced by DEA/NO was found to be uncoupled from its contractile effects. However, hearts treated with DEA/NO (10 µM) showed a significant increase (1.4-fold; P < 0.01) in troponin I phosphorylation compared to control, untreated hearts. These results suggest that the reduction in myofilament Ca²⁺ responsiveness produced by DEA/NO results from phosphorylation of troponin I by PKG.

This article has been cited by other articles:

				S. W. Rabkin and M. Y. C. Tsang The action of nitric oxide to enhance cell survival in chick cardiomyocytes is mediated through a cGMP and ERK1/2 pathway while p38 mitogen-activated protein kinase-dependent pathways do not alter cell death Exp Physiol, July 1, 2008; 93(7): 834 - 842. [Abstract] [Full Text] [PDF]

				P. J. Leary, S. Rajasekaran, R. R. Morrison, E. I. Tuomanen, T. K. Chin, and P. A. Hofmann A cardioprotective role for platelet-activating factor through NOS-dependent S-nitrosylation Am J Physiol Heart Circ Physiol, June 1, 2008; 294(6): H2775 - H2784. [Abstract] [Full Text] [PDF]

				N. Fukuda, J. O-Uchi, and S. Kurihara Neuronal NO Synthase-Derived NO: A Novel Relaxing Factor in Myocardium? Circ. Res., February 1, 2008; 102(2): 148 - 150. [Full Text] [PDF]

				Y. H. Zhang, M. H. Zhang, C. E. Sears, K. Emanuel, C. Redwood, A. El-Armouche, E. G. Kranias, and B. Casadei Reduced Phospholamban Phosphorylation Is Associated With Impaired Relaxation in Left Ventricular Myocytes From Neuronal NO Synthase-Deficient Mice Circ. Res., February 1, 2008; 102(2): 242 - 249. [Abstract] [Full Text] [PDF]

				D. A. Kass, H. C. Champion, and J. A. Beavo Phosphodiesterase Type 5: Expanding Roles in Cardiovascular Regulation Circ. Res., November 26, 2007; 101(11): 1084 - 1095. [Abstract] [Full Text] [PDF]

				F. Vandeput, S. L. Wolda, J. Krall, R. Hambleton, L. Uher, K. N. McCaw, P. B. Radwanski, V. Florio, and M. A. Movsesian Cyclic Nucleotide Phosphodiesterase PDE1C1 in Human Cardiac Myocytes J. Biol. Chem., November 9, 2007; 282(45): 32749 - 32757. [Abstract] [Full Text] [PDF]

				S. N. Mink, Z.-Q. Cheng, R. Bose, H. Jacobs, K. Kasian, D. E. Roberts, L. E. Santos-Martinez, and R. B. Light Lysozyme, a mediator of sepsis, impairs the cardiac neural adrenergic response by nonendothelial release of NO and inhibitory G protein signaling Am J Physiol Heart Circ Physiol, November 1, 2007; 293(5): H3140 - H3149. [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]

				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]

				M. Zaccolo and M. A. Movsesian cAMP and cGMP Signaling Cross-Talk: Role of Phosphodiesterases and Implications for Cardiac Pathophysiology Circ. Res., June 8, 2007; 100(11): 1569 - 1578. [Abstract] [Full Text] [PDF]

				T. Dai, Y. Tian, C. G. Tocchetti, T. Katori, A. M. Murphy, D. A. Kass, N. Paolocci, and W. D. Gao Nitroxyl increases force development in rat cardiac muscle J. Physiol., May 1, 2007; 580(3): 951 - 960. [Abstract] [Full Text] [PDF]

				E. Takimoto, D. Belardi, C. G. Tocchetti, S. Vahebi, G. Cormaci, E. A. Ketner, A. L. Moens, H. C. Champion, and D. A. Kass Compartmentalization of Cardiac {beta}-Adrenergic Inotropy Modulation by Phosphodiesterase Type 5 Circulation, April 24, 2007; 115(16): 2159 - 2167. [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]

				P. Cabrales, J. Martini, M. Intaglietta, and A. G. Tsai Blood viscosity maintains microvascular conditions during normovolemic anemia independent of blood oxygen-carrying capacity Am J Physiol Heart Circ Physiol, August 1, 2006; 291(2): H581 - H590. [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]

				R. Hambleton, J. Krall, E. Tikishvili, M. Honeggar, F. Ahmad, V. C. Manganiello, and M. A. Movsesian Isoforms of Cyclic Nucleotide Phosphodiesterase PDE3 and Their Contribution to cAMP Hydrolytic Activity in Subcellular Fractions of Human Myocardium J. Biol. Chem., November 25, 2005; 280(47): 39168 - 39174. [Abstract] [Full Text] [PDF]

				J. Lindenfeld, J. V. Weil, V. L. Travis, and L. D. Horwitz Regulation of oxygen delivery during induced polycythemia in exercising dogs Am J Physiol Heart Circ Physiol, November 1, 2005; 289(5): H1821 - H1825. [Abstract] [Full Text] [PDF]

				M. J. Semigran Type 5 Phosphodiesterase Inhibition: The Focus Shifts to the Heart Circulation, October 25, 2005; 112(17): 2589 - 2591. [Full Text] [PDF]

				X.-W. Yu, M.-Y. G Liu, R. H Kennedy, and S. J Liu Both cGMP and peroxynitrite mediate chronic interleukin-6-induced negative inotropy in adult rat ventricular myocytes J. Physiol., July 15, 2005; 566(2): 341 - 353. [Abstract] [Full Text] [PDF]

				J. Su, P. M. Scholz, and H. R. Weiss Differential Effects of cGMP Produced by Soluble and Particulate Guanylyl Cyclase on Mouse Ventricular Myocytes Experimental Biology and Medicine, April 1, 2005; 230(4): 242 - 250. [Abstract] [Full Text] [PDF]

				J. Layland, R. J. Solaro, and A. M. Shah Regulation of cardiac contractile function by troponin I phosphorylation Cardiovasc Res, April 1, 2005; 66(1): 12 - 21. [Abstract] [Full Text] [PDF]

				E. Takimoto, H. C. Champion, D. Belardi, J. Moslehi, M. Mongillo, E. Mergia, D. C. Montrose, T. Isoda, K. Aufiero, M. Zaccolo, et al. cGMP Catabolism by Phosphodiesterase 5A Regulates Cardiac Adrenergic Stimulation by NOS3-Dependent Mechanism Circ. Res., January 7, 2005; 96(1): 100 - 109. [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]

				Q. Qin, X.-M. Yang, L. Cui, S. D. Critz, M. V. Cohen, N. C. Browner, T. M. Lincoln, and J. M. Downey Exogenous NO triggers preconditioning via a cGMP- and mitoKATP-dependent mechanism Am J Physiol Heart Circ Physiol, August 1, 2004; 287(2): H712 - H718. [Abstract] [Full Text] [PDF]

				J. Layland, D. J. Grieve, A. C. Cave, E. Sparks, R J. Solaro, and A. M. Shah Essential role of troponin I in the positive inotropic response to isoprenaline in mouse hearts contracting auxotonically J. Physiol., May 1, 2004; 556(3): 835 - 847. [Abstract] [Full Text] [PDF]

				H. C. Champion, D. Georgakopoulos, E. Takimoto, T. Isoda, Y. Wang, and D. A. Kass Modulation of In Vivo Cardiac Function by Myocyte-Specific Nitric Oxide Synthase-3 Circ. Res., March 19, 2004; 94(5): 657 - 663. [Abstract] [Full Text] [PDF]

				P.B. Massion, O. Feron, C. Dessy, and J.-L. Balligand Nitric Oxide and Cardiac Function: Ten Years After, and Continuing Circ. Res., September 5, 2003; 93(5): 388 - 398. [Abstract] [Full Text] [PDF]

				A. Haase and G. Bicker Nitric oxide and cyclic nucleotides are regulators of neuronal migration in an insect embryo Development, September 1, 2003; 130(17): 3977 - 3987. [Abstract] [Full Text] [PDF]

				C. Martin, R. Schulz, H. Post, P. Gres, and G. Heusch Effect of NO synthase inhibition on myocardial metabolism during moderate ischemia Am J Physiol Heart Circ Physiol, June 1, 2003; 284(6): H2320 - H2324. [Abstract] [Full Text] [PDF]

				N. Paolocci, T. Katori, H. C. Champion, M. E. St. John, K. M. Miranda, J. M. Fukuto, D. A. Wink, and D. A. Kass From the Cover: Positive inotropic and lusitropic effects of HNO/NO- in failing hearts: Independence from beta -adrenergic signaling PNAS, April 29, 2003; 100(9): 5537 - 5542. [Abstract] [Full Text] [PDF]

				G. Boerrigter, L. C. Costello-Boerrigter, A. Cataliotti, T. Tsuruda, G. J. Harty, H. Lapp, J.-P. Stasch, and J. C. Burnett Jr Cardiorenal and Humoral Properties of a Novel Direct Soluble Guanylate Cyclase Stimulator BAY 41-2272 in Experimental Congestive Heart Failure Circulation, February 11, 2003; 107(5): 686 - 689. [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]