Circulation Research, Vol 74, 970-978, Copyright © 1994 by American Heart Association

ARTICLES

8-bromo-cGMP reduces the myofilament response to Ca2+ in intact cardiac myocytes

AM Shah, HA Spurgeon, SJ Sollott, A Talo and EG Lakatta
Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224.

The role of cGMP in myocardial contraction is not established. Recent reports suggest that nitric oxide, released by endothelial cells or within myocytes, modifies myocardial contraction by raising cGMP. We studied the effects of 8-bromo-cGMP (8bcGMP, 50 mumol/L) on contraction (cell shortening) and simultaneous intracellular Ca2+ transients (indo 1 fluorescence ratio) in intact adult rat ventricular myocytes (0.5 Hz and 25 degrees C) 8bcGMP reduced myocyte twitch amplitude and time to peak shortening (-19.6 +/- 4.2% and -17.6 +/- 1.3%, respectively) and increased steady-state diastolic cell length (+0.6 +/- 0.1 microns, mean +/- SEM, n = 8; all P < .05) but had no effect on shortening velocity, systolic or diastolic fluorescence ratio, or time to peak fluorescence ratio (all P = NS). In 7 of 13 myocytes, this negative inotropic effect was preceded by a transient positive inotropic effect, with small increases in twitch amplitude, shortening velocity, and cytosolic Ca2+ transient. Analysis of 8bcGMP effects on both the dynamic and steady-state relation between cell shortening and intracellular Ca2+ (during twitch contraction and tetanic contraction, respectively) indicated reduction in the myofilament response to Ca2+ in all cases. These 8bcGMP effects were inhibited by KT5823 (1 mumol/L), an inhibitor of cGMP-dependent protein kinase, or by the presence of isoproterenol (3 nmol/L). 8bcGMP had no effect on cytosolic pH in cells (n = 4) loaded with the fluorescent probe carboxyseminaphthorhodafluor-1. These data indicate that cGMP may modulate myocardial relaxation and diastolic tone by reducing the relative myofilament response to Ca2+, probably via cGMP-dependent protein kinase.

This article has been cited by other articles:

				E. S. Buys, A. Cauwels, M. J. Raher, J. J. Passeri, I. Hobai, S. M. Cawley, K. M. Rauwerdink, H. Thibault, P. Y. Sips, R. Thoonen, et al. sGC{alpha}1{beta}1 attenuates cardiac dysfunction and mortality in murine inflammatory shock models Am J Physiol Heart Circ Physiol, August 1, 2009; 297(2): H654 - H663. [Abstract] [Full Text] [PDF]

				J. Inserte, J. A. Barrabes, V. Hernando, and D. Garcia-Dorado Orphan targets for reperfusion injury Cardiovasc Res, July 15, 2009; 83(2): 169 - 178. [Abstract] [Full Text] [PDF]

				P. Castro-Chaves, R. Fontes-Carvalho, M. Pintalhao, P. Pimentel-Nunes, and A. F. Leite-Moreira Angiotensin II-induced increase in myocardial distensibility and its modulation by the endocardial endothelium in the rabbit heart Exp Physiol, June 1, 2009; 94(6): 665 - 674. [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]

				M. Kruger, S. Kotter, A. Grutzner, P. Lang, C. Andresen, M. M. Redfield, E. Butt, C. G. dos Remedios, and W. A. Linke Protein Kinase G Modulates Human Myocardial Passive Stiffness by Phosphorylation of the Titin Springs Circ. Res., January 2, 2009; 104(1): 87 - 94. [Abstract] [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]

				S. Moniotte, C. Belge, B. Sekkali, P.B. Massion, B. Rozec, C. Dessy, and J.-L. Balligand Sepsis is associated with an upregulation of functional {beta}3 adrenoceptors in the myocardium Eur J Heart Fail, December 1, 2007; 9(12): 1163 - 1171. [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]

				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]

				D. Garcia-Dorado, A. Rodriguez-Sinovas, M. Ruiz-Meana, J. Inserte, L. Agullo, and A. Cabestrero The end-effectors of preconditioning protection against myocardial cell death secondary to ischemia-reperfusion Cardiovasc Res, May 1, 2006; 70(2): 274 - 285. [Abstract] [Full Text] [PDF]

				S. R. Martin, K. Emanuel, C. E. Sears, Y.-H. Zhang, and B. Casadei Are myocardial eNOS and nNOS involved in the {beta}-adrenergic and muscarinic regulation of inotropy? A systematic investigation Cardiovasc Res, April 1, 2006; 70(1): 97 - 106. [Abstract] [Full Text] [PDF]

				J. B. Patel, M. L. Valencik, A. M. Pritchett, J. C. Burnett Jr., J. A. McDonald, and M. M. Redfield Cardiac-specific attenuation of natriuretic peptide A receptor activity accentuates adverse cardiac remodeling and mortality in response to pressure overload Am J Physiol Heart Circ Physiol, August 1, 2005; 289(2): H777 - H784. [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]

				Y. Abdallah, A. Gkatzoflia, H. Pieper, E. Zoga, S. Walther, S. Kasseckert, M. Schafer, K.D. Schluter, H.M. Piper, and C. Schafer Mechanism of cGMP-mediated protection in a cellular model of myocardial reperfusion injury Cardiovasc Res, April 1, 2005; 66(1): 123 - 131. [Abstract] [Full Text] [PDF]

				J. K. Bendall, T. Damy, P. Ratajczak, X. Loyer, V. Monceau, I. Marty, P. Milliez, E. Robidel, F. Marotte, J.-L. Samuel, et al. Role of Myocardial Neuronal Nitric Oxide Synthase-Derived Nitric Oxide in {beta}-Adrenergic Hyporesponsiveness After Myocardial Infarction-Induced Heart Failure in Rat Circulation, October 19, 2004; 110(16): 2368 - 2375. [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]

				R. Rodriguez, B. Molino, H. R. Weiss, and P. M. Scholz Negative metabolic and coronary flow effects of decreases in cAMP and increases in cGMP in control and renal hypertensive rabbit hearts J Appl Physiol, July 1, 2004; 97(1): 439 - 445. [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]

				A. Adler, H. Huang, Z. Wang, J. Conetta, E. Levee, X. Zhang, and T. H. Hintze Endocardial endothelium in the avascular frog heart: role for diffusion of NO in control of cardiac O2 consumption Am J Physiol Heart Circ Physiol, July 1, 2004; 287(1): H14 - H21. [Abstract] [Full Text] [PDF]

				D. A. Kass, J. G.F. Bronzwaer, and W. J. Paulus What Mechanisms Underlie Diastolic Dysfunction in Heart Failure? Circ. Res., June 25, 2004; 94(12): 1533 - 1542. [Abstract] [Full Text] [PDF]

				T. Tatsumi, N. Keira, K. Akashi, M. Kobara, S. Matoba, J. Shiraishi, S. Yamanaka, A. Mano, M. Takeda, S. Nishikawa, et al. Nitric oxide-cGMP pathway is involved in endotoxin-induced contractile dysfunction in rat hearts J Appl Physiol, March 1, 2004; 96(3): 853 - 860. [Abstract] [Full Text] [PDF]

				R. Schulz, M. Kelm, and G. Heusch Nitric oxide in myocardial ischemia/reperfusion injury Cardiovasc Res, February 15, 2004; 61(3): 402 - 413. [Abstract] [Full Text] [PDF]

				Y. Ohsawa, H. Toko, M. Katsura, K. Morimoto, H. Yamada, Y. Ichikawa, T. Murakami, S. Ohkuma, I. Komuro, and Y. Sunada Overexpression of P104L mutant caveolin-3 in mice develops hypertrophic cardiomyopathy with enhanced contractility in association with increased endothelial nitric oxide synthase activity Hum. Mol. Genet., January 15, 2004; 13(2): 151 - 157. [Abstract] [Full Text] [PDF]

				K. Sangawa, K. Nakanishi, K. Ishino, M. Inoue, M. Kawada, and S. Sano Atrial natriuretic peptide protects against ischemia-reperfusion injury in the isolated rat heart Ann. Thorac. Surg., January 1, 2004; 77(1): 233 - 237. [Abstract] [Full Text] [PDF]

				J. Su, S. Zhang, J. Tse, P. M. Scholz, and H. R. Weiss Alterations in nitric oxide-cGMP pathway in ventricular myocytes from obese leptin-deficient mice Am J Physiol Heart Circ Physiol, November 1, 2003; 285(5): H2111 - H2117. [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]

				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]

				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]

				P B Massion and J-L Balligand Modulation of cardiac contraction, relaxation and rate by the endothelial nitric oxide synthase (eNOS): lessons from genetically modified mice J. Physiol., January 1, 2003; 546(1): 63 - 75. [Abstract] [Full Text] [PDF]

				F. Brunner, R. Maier, P. Andrew, G. Wolkart, R. Zechner, and B. Mayer Attenuation of myocardial ischemia/reperfusion injury in mice with myocyte-specific overexpression of endothelial nitric oxide synthase Cardiovasc Res, January 1, 2003; 57(1): 55 - 62. [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]

				E. A. Ashley, C. E. Sears, S. M. Bryant, H. C. Watkins, and B. Casadei Cardiac Nitric Oxide Synthase 1 Regulates Basal and {beta}-Adrenergic Contractility in Murine Ventricular Myocytes Circulation, June 25, 2002; 105(25): 3011 - 3016. [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. 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]

				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]

				K. C. Wollert, B. Fiedler, S. Gambaryan, A. Smolenski, J. Heineke, E. Butt, C. Trautwein, S. M. Lohmann, and H. Drexler Gene Transfer of cGMP-Dependent Protein Kinase I Enhances the Antihypertrophic Effects of Nitric Oxide in Cardiomyocytes Hypertension, January 1, 2002; 39(1): 87 - 92. [Abstract] [Full Text] [PDF]

				M. T. Ziolo, H. Katoh, and D. M. Bers Positive and negative effects of nitric oxide on Ca2+ sparks: influence of beta -adrenergic stimulation Am J Physiol Heart Circ Physiol, December 1, 2001; 281(6): H2295 - H2303. [Abstract] [Full Text] [PDF]

				T. Noguchi, Z. Chen, S. P. Bell, L. Nyland, and M. M. LeWinter Activation of PKC decreases myocardial O2 consumption and increases contractile efficiency in rats Am J Physiol Heart Circ Physiol, November 1, 2001; 281(5): H2191 - H2197. [Abstract] [Full Text] [PDF]

				F. Padilla, D. Garcia-Dorado, L. Agullo, J. A Barrabes, J. Inserte, N. Escalona, M. Meyer, M. Mirabet, P. Pina, and J. Soler-Soler Intravenous administration of the natriuretic peptide urodilatin at low doses during coronary reperfusion limits infarct size in anesthetized pigs Cardiovasc Res, August 15, 2001; 51(3): 592 - 600. [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]

				C. Y. T. Hart, E. L. Hahn, D. M. Meyer, J. C. Burnett Jr., and M. M. Redfield Differential effects of natriuretic peptides and NO on LV function in heart failure and normal dogs Am J Physiol Heart Circ Physiol, July 1, 2001; 281(1): H146 - H154. [Abstract] [Full Text] [PDF]

				G. Vandecasteele, I. Verde, C. Rucker-Martin, P. Donzeau-Gouge, and R. Fischmeister Cyclic GMP regulation of the L-type Ca2+ channel current in human atrial myocytes J. Physiol., June 1, 2001; 533(2): 329 - 340. [Abstract] [Full Text] [PDF]

				A. Godecke, T. Heinicke, A. Kamkin, I. Kiseleva, R. H Strasser, U. K M Decking, T. Stumpe, G. Isenberg, and J. Schrader Inotropic response to {beta}-adrenergic receptor stimulation and anti-adrenergic effect of ACh in endothelial NO synthase-deficient mouse hearts J. Physiol., April 1, 2001; 532(1): 195 - 204. [Abstract] [Full Text] [PDF]

				B. TAVERNIER, A. MEBAZAA, P. MATEO, S. SYS, R. VENTURA-CLAPIER, and V. VEKSLER Phosphorylation-dependent Alteration in Myofilament Ca2+ Sensitivity but Normal Mitochondrial Function in Septic Heart Am. J. Respir. Crit. Care Med., February 1, 2001; 163(2): 362 - 367. [Abstract] [Full Text]

				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]

				M. G V. Petroff, E. A Aiello, J. Palomeque, M. A Salas, and A. Mattiazzi Subcellular mechanisms of the positive inotropic effect of angiotensin II in cat myocardium J. Physiol., November 15, 2000; 529(1): 189 - 203. [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]

				H.-L. Pan, S.-R. Chen, G. M. Scicli, and O. A. Carretero Cardiac interstitial bradykinin release during ischemia is enhanced by ischemic preconditioning Am J Physiol Heart Circ Physiol, July 1, 2000; 279(1): H116 - H121. [Abstract] [Full Text] [PDF]

				W. W. Brooks, O. H. L. Bing, M. O. Boluyt, A. Malhotra, J. P. Morgan, N. Satoh, W. S. Colucci, and C. H. Conrad Altered Inotropic Responsiveness and Gene Expression of Hypertrophied Myocardium With Captopril Hypertension, June 1, 2000; 35(6): 1203 - 1209. [Abstract] [Full Text] [PDF]

				T. Tatsumi, S. Matoba, A. Kawahara, N. Keira, J. Shiraishi, K. Akashi, M. Kobara, T. Tanaka, M. Katamura, C. Nakagawa, et al. Cytokine-induced nitric oxide production inhibits mitochondrial energy production and impairs contractile function in rat cardiac myocytes J. Am. Coll. Cardiol., April 1, 2000; 35(5): 1338 - 1346. [Abstract] [Full Text] [PDF]

				J. Bartunek, E. O. Weinberg, M. Tajima, S. Rohrbach, S. E. Katz, P. S. Douglas, and B. H. Lorell Chronic NG-Nitro-L-Arginine Methyl Ester-Induced Hypertension : Novel Molecular Adaptation to Systolic Load in Absence of Hypertrophy Circulation, February 1, 2000; 101(4): 423 - 429. [Abstract] [Full Text] [PDF]

				J. Inserte, D. Garcia-Dorado, L. Agullo, A. Paniagua, and J. Soler-Soler Urodilatin limits acute reperfusion injury in the isolated rat heart Cardiovasc Res, January 14, 2000; 45(2): 351 - 359. [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]

				K. Yuasa, H. Michibata, K. Omori, and N. Yanaka A Novel Interaction of cGMP-dependent Protein Kinase I with Troponin T J. Biol. Chem., December 24, 1999; 274(52): 37429 - 37434. [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]

				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]

				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]

				C. M. Matter, L. Mandinov, P. A. Kaufmann, G. Vassalli, Z. Jiang, and O. M. Hess Effect of NO Donors on LV Diastolic Function in Patients With Severe Pressure-Overload Hypertrophy Circulation, May 11, 1999; 99(18): 2396 - 2401. [Abstract] [Full Text] [PDF]

				L. Agullo, D. Garcia-Dorado, J. Inserte, A. Paniagua, P. Pyrhonen, J. Llevadot, and J. Soler-Soler L-Arginine limits myocardial cell death secondary to hypoxia-reoxygenation by a cGMP-dependent mechanism Am J Physiol Heart Circ Physiol, May 1, 1999; 276(5): H1574 - H1580. [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]

				S. Matoba, T. Tatsumi, N. Keira, A. Kawahara, K. Akashi, M. Kobara, J. Asayama, and M. Nakagawa Cardioprotective Effect of Angiotensin-Converting Enzyme Inhibition Against Hypoxia/Reoxygenation Injury in Cultured Rat Cardiac Myocytes Circulation, February 16, 1999; 99(6): 817 - 822. [Abstract] [Full Text] [PDF]

				Z.-K. Yang, N. J. Draper, and A. M. Shah Ca2+-independent inhibition of myocardial contraction by coronary effluent of hypoxic rat hearts Am J Physiol Heart Circ Physiol, February 1, 1999; 276(2): H623 - H632. [Abstract] [Full Text] [PDF]

				A. Kumar, R. Brar, P. Wang, L. Dee, G. Skorupa, F. Khadour, R. Schulz, and J. E. Parrillo Role of nitric oxide and cGMP in human septic serum-induced depression of cardiac myocyte contractility Am J Physiol Regulatory Integrative Comp Physiol, January 1, 1999; 276(1): R265 - R276. [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]

				H. Drexler, S. Kastner, A. Strobel, R. Studer, O. E. Brodde, and G. Hasenfuss Expression, activity and functional significance of inducible nitric oxide synthase in the failing human heart J. Am. Coll. Cardiol., October 1, 1998; 32(4): 955 - 963. [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]

				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]

				B. Tavernier, D. Garrigue, C. Boulle, B. Vallet, and P. Adnet Myofilament calcium sensitivity is decreased in skinned cardiac fibres of endotoxin-treated rabbits Cardiovasc Res, May 1, 1998; 38(2): 472 - 479. [Abstract] [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]

				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]

				L. Protas, J.-B. Shen, and A. J. Pappano Carbachol Increases Contractions and Intracellular Ca++ Transients in Guinea Pig Ventricular Myocytes J. Pharmacol. Exp. Ther., January 1, 1998; 284(1): 66 - 74. [Abstract] [Full Text]

				S. Yasuda and W. Y. W. Lew Lipopolysaccharide Depresses Cardiac Contractility and ß-Adrenergic Contractile Response by Decreasing Myofilament Response to Ca2+ in Cardiac Myocytes Circ. Res., December 19, 1997; 81(6): 1011 - 1020. [Abstract] [Full Text]

				J. D. Sadoff, P. M. Scholz, J. Tse, and H. R. Weiss Reduced myocardial cyclic GMP increases myocardial O2 consumption in control but not renal hypertension-induced cardiac hypertrophy Cardiovasc Res, December 1, 1997; 36(3): 453 - 459. [Abstract] [Full Text] [PDF]

				W. J. Paulus, S. Kastner, P. Pujadas, A. M. Shah, H. Drexler, and M. Vanderheyden Left Ventricular Contractile Effects of Inducible Nitric Oxide Synthase in the Human Allograft Circulation, November 18, 1997; 96(10): 3436 - 3442. [Abstract] [Full Text]

				K. Yamamoto, J. C. Burnett Jr., and M. M. Redfield Effect of endogenous natriuretic peptide system on ventricular and coronary function in failing heart Am J Physiol Heart Circ Physiol, November 1, 1997; 273(5): H2406 - H2414. [Abstract] [Full Text] [PDF]

				C. F. McTiernan, B. H. Lemster, C. Frye, S. Brooks, A. Combes, and A. M. Feldman Interleukin-1ß Inhibits Phospholamban Gene Expression in Cultured Cardiomyocytes Circ. Res., October 19, 1997; 81(4): 493 - 503. [Abstract] [Full Text]

				M. Straznicka, G. Gong, J. Tse, P. M. Scholz, and H. R. Weiss cGMP level that reduces cardiac myocyte O2 consumption is altered in renal hypertension Am J Physiol Heart Circ Physiol, October 1, 1997; 273(4): H1949 - H1955. [Abstract] [Full Text] [PDF]

				D. J. Pinsky, S. Patton, S. Mesaros, V. Brovkovych, E. Kubaszewski, S. Grunfeld, and T. Malinski Mechanical Transduction of Nitric Oxide Synthesis in the Beating Heart Circ. Res., September 19, 1997; 81(3): 372 - 379. [Abstract] [Full Text]

				B. D. Prendergast, B M. Sci, V. F. Sagach, and A. M. Shah Basal Release of Nitric Oxide Augments the Frank-Starling Response in the Isolated Heart Circulation, August 19, 1997; 96(4): 1320 - 1329. [Abstract] [Full Text]

				M. Flesch, H. Kilter, B. Cremers, O. Lenz, M. Südkamp, F. Kuhn-Regnier, and M. Böhm J. Pharmacol. Exp. Ther., June 1, 1997; 281(3): 1340 - 1349. [Abstract] [Full Text]

				A. M. Shah, A. Mebazaa, Z.-K. Yang, G. Cuda, E. B. Lankford, C. B. Pepper, S. J. Sollott, J. R. Sellers, J. L. Robotham, and E. G. Lakatta Inhibition of Myocardial Crossbridge Cycling by Hypoxic Endothelial Cells : A Potential Mechanism for Matching Oxygen Supply and Demand? Circ. Res., May 19, 1997; 80(5): 688 - 698. [Abstract] [Full Text]

				N. Ito, J. Bartunek, K. W. Spitzer, and B. H. Lorell Effects of the Nitric Oxide Donor Sodium Nitroprusside on Intracellular pH and Contraction in Hypertrophied Myocytes Circulation, May 6, 1997; 95(9): 2303 - 2311. [Abstract] [Full Text]

				H. Ikenouchi, K. Kangawa, H. Matsuo, and Y. Hirata Negative Inotropic Effect of Adrenomedullin in Isolated Adult Rabbit Cardiac Ventricular Myocytes Circulation, May 6, 1997; 95(9): 2318 - 2324. [Abstract] [Full Text]

				A. J. Sherman, C. A. Davis III, F. J. Klocke, K. R. Harris, G. Srinivasan, A. S. Yaacoub, D. A. Quinn, K. A. Ahlin, and J. J. Jang Blockade of Nitric Oxide Synthesis Reduces Myocardial Oxygen Consumption In Vivo Circulation, March 4, 1997; 95(5): 1328 - 1334. [Abstract] [Full Text]

				R. A. Kelly and T. W. Smith Cytokines and Cardiac Contractile Function Circulation, February 18, 1997; 95(4): 778 - 781. [Full Text]

				J. Bartunek, A. M. Shah, M. Vanderheyden, and W. J. Paulus Dobutamine Enhances Cardiodepressant Effects of Receptor-Mediated Coronary Endothelial Stimulation Circulation, January 7, 1997; 95(1): 90 - 96. [Abstract] [Full Text]

				R. A. Kelly, J.-L. Balligand, and T. W. Smith Nitric Oxide and Cardiac Function Circ. Res., September 1, 1996; 79(3): 363 - 380. [Full Text]

				P. Mohan, D. L. Brutsaert, W. J. Paulus, and S. U. Sys Myocardial Contractile Response to Nitric Oxide and cGMP Circulation, March 15, 1996; 93(6): 1223 - 1229. [Abstract] [Full Text]

				D. M. Kaye, S. D. Wiviott, J.-L. Balligand, W. W. Simmons, T. W. Smith, and R. A. Kelly Frequency-Dependent Activation of a Constitutive Nitric Oxide Synthase and Regulation of Contractile Function in Adult Rat Ventricular Myocytes Circ. Res., February 1, 1996; 78(2): 217 - 224. [Abstract] [Full Text]

				K. Node, M. Kitakaze, H. Kosaka, K. Komamura, T. Minamino, M. Inoue, M. Tada, M. Hori, and T. Kamada Increased Release of NO During Ischemia Reduces Myocardial Contractility and Improves Metabolic Dysfunction Circulation, January 15, 1996; 93(2): 356 - 364. [Abstract] [Full Text]

				P. B. Anning, R. M. Grocott-Mason, M. J. Lewis, and A. M. Shah Enhancement of Left Ventricular Relaxation in the Isolated Heart by an Angiotensin-Converting Enzyme Inhibitor Circulation, November 1, 1995; 92(9): 2660 - 2665. [Abstract] [Full Text]

				W. J. Paulus, P. J. Vantrimpont, and A. M. Shah Paracrine Coronary Endothelial Control of Left Ventricular Function in Humans Circulation, October 15, 1995; 92(8): 2119 - 2126. [Abstract] [Full Text]

				G. W. De Keulenaer, L. J. Andries, S. U. Sys, and D. L. Brutsaert Endothelin-Mediated Positive Inotropic Effect Induced by Reactive Oxygen Species in Isolated Cardiac Muscle Circ. Res., May 1, 1995; 76(5): 878 - 884. [Abstract] [Full Text]