Evaluation of the therapeutic utility of phosphodiesterase 5A inhibition in the mdx mouse model of duchenne muscular dystrophy

Handbook of Experimental Pharmacology

Volumn 204, Issue , 2011, Pages 323-344

  Percival, Justin M ^a   Adamo, Candace M ^b   Beavo, Joseph A ^b   Froehner, Stanley C ^a  

^a UNIVERSITY OF WASHINGTON   (United States)

^b UNIVERSITY OF WASHINGTON SCHOOL OF MEDICINE   (United States)

Author keywords

Cardiac muscle; Cardiomyopathy; cGMP; Duchenne Muscular Dystrophy; Dystrophin; Mdx; Neuronal nitric oxide synthase; Nitric oxide; nNOS; PDE5; PDE5 inhibitors; Sildenafil; Skeletal muscle

Indexed keywords

GUANOSINE TRIPHOSPHATE; NEURONAL NITRIC OXIDE SYNTHASE; PHOSPHODIESTERASE 5A; PHOSPHODIESTERASE V; RYANODINE RECEPTOR 2; SILDENAFIL; TADALAFIL; UNCLASSIFIED DRUG; VARDENAFIL; CYCLIC GMP; NITRIC OXIDE; PDE5A PROTEIN, MOUSE; PHOSPHODIESTERASE V INHIBITOR;

BINDING SITE; CALCIUM TRANSPORT; DRUG ACTIVITY; DRUG EFFICACY; DRUG POTENCY; DRUG SAFETY; DUCHENNE MUSCULAR DYSTROPHY; ECHOCARDIOGRAPHY; ENZYME INHIBITION; GLUCOSE HOMEOSTASIS; GLUCOSE METABOLISM; GLUCOSE TRANSPORT; HEART MUSCLE; HEART MUSCLE CONTRACTILITY; HEART PROTECTION; HEART VENTRICLE COMPLIANCE; HUMAN; HYDROLYSIS; MEMBRANE PERMEABILITY; MOLECULAR DYNAMICS; MUSCLE CONTRACTION; NONHUMAN; OXIDATIVE PHOSPHORYLATION; PATHOGENESIS; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN DEGRADATION; PROTEIN EXPRESSION; PROTEIN LOCALIZATION; REVIEW; SIGNAL TRANSDUCTION; SKELETAL MUSCLE; ANIMAL; ARTICLE; DISEASE MODEL; ENZYMOLOGY; HEART MUSCLE CELL; MOUSE; PHYSIOLOGY; X CHROMOSOME LINKED MUSCULAR DYSTROPHIC MOUSE;

ANIMALS; CYCLIC GMP; CYCLIC NUCLEOTIDE PHOSPHODIESTERASES, TYPE 5; DISEASE MODELS, ANIMAL; MICE; MICE, INBRED MDX; MUSCLE, SKELETAL; MUSCULAR DYSTROPHY, DUCHENNE; MYOCYTES, CARDIAC; NITRIC OXIDE; NITRIC OXIDE SYNTHASE TYPE I; PHOSPHODIESTERASE 5 INHIBITORS; SIGNAL TRANSDUCTION;

EID: 79960900670     PISSN: 01712004     EISSN: 18650325     Source Type: Book Series    
DOI: 10.1007/978-3-642-17969-3_14     Document Type: Review

References (93)

1. Adamo CM, Dai DF, Percival JM, Minami E, Willis MS, Patrucco E, Froehner SC, Beavo JA (2010) Sildenafil reverses cardiac dysfunction in the mdx mouse model of Duchenne muscular dystrophy. Proc Natl Acad Sci USA 107:19079-19083
2. Adams ME, Kramarcy N, Krall SP, Rossi SG, Rotundo RL, Sealock R, Froehner SC (2000) Absence of alpha-syntrophin leads to structurally aberrant neuromuscular synapses deficient in utrophin. J Cell Biol 150:1385-1398
3. Adams ME, Mueller HA, Froehner SC (2001) In vivo requirement of the alpha-syntrophin PDZ domain for the sarcolemmal localization of nNOS and aquaporin-4. J Cell Biol 155:113-122 (Pubitemid 34286212)
4. Asai A, Sahani N, Kaneki M, Ouchi Y, Martyn JA, Yasuhara SE (2007) Primary role of functional ischemia, quantitative evidence for the two-hit mechanism, and phospho-diesterase-5 inhibitor therapy in mouse muscular dystrophy. PLoS One 2:e806
5. Barouch LA, Harrison RW, Skaf MW, Rosas GO, Cappola TP, Kobeissi ZA, Hobai IA, Lemmon CA, Burnett AL, ORourke B, Rodriguez ER, Huang PL, Lima JA, Berkowitz DE, Hare JM (2002) Nitric oxide regulates the heart by spatial confinement of nitric oxide synthase isoforms. Nature 416:337-339
6. Bendall JK, Damy T, Ratajczak P, Loyer X, Monceau V, Marty I, Milliez P, Robidel E, Marotte F, Samuel JL, Heymes C (2004) Role of myocardial neuronal nitric oxide synthase-derived nitric oxide in beta-adrenergic hyporesponsiveness after myocardial infarction-induced heart failure in rat. Circulation 110:2368-2375 (Pubitemid 39407341)
7. Bender AT, Beavo JA (2006) Cyclic nucleotide phosphodiesterases: molecular regulation to clinical use. Pharmacol Rev 58:488-520 (Pubitemid 44394910)
8. Bia BL, Cassidy PJ, Young ME, Rafael JA, Leighton B, Davies KE, Radda GK, Clarke K (1999) Decreased myocardial nNOS, increased iNOS and abnormal ECGs in mouse models of Duchenne muscular dystrophy. J Mol Cell Cardiol 31:1857-1862 (Pubitemid 29458703)
9. Bloom TJ (2002) Cyclic nucleotide phosphodiesterase isozymes expressed in mouse skeletal muscle. Can J Physiol Pharmacol 80:1132-1135 (Pubitemid 36249893)
10. Bostick B, Yue Y, Long C, Marschalk N, Fine DM, Chen J, Duan D (2009) Cardiac expression of a mini-dystrophin that normalizes skeletal muscle force only partially restores heart function in aged mdx mice. Mol Ther 17:253-261
11. Boulanger CM, Heymes C, Benessiano J, Geske RS, Lévy BI, Vanhoutte PM (1998) Neuronal nitric oxide synthase is expressed in rat vascular smooth muscle cells: activation by angiotensin II in hypertension. Circ Res 83:1271-1278 (Pubitemid 29006042)
12. Bredt DS, Snyder SH (1990) Isolation of nitric oxide synthetase, a calmodulin-requiring enzyme. Proc Natl Acad Sci USA 87:682-685
13. Brenman JE, Chao DS, Xia H, Aldape K, Bredt DS (1995) Nitric oxide synthase complexed with dystrophin and absent from skeletal muscle sarcolemma in Duchenne muscular dystrophy. Cell 82:743-752
14. Brenman JE, Chao DS, Gee SH, McGee AW, Craven SE, Santillano DR, Wu Z, Huang F, Xia H, Peters MF, Froehner SC, Bredt DS (1996) Interaction of nitric oxide synthase with the postsynaptic density protein PSD-95 and alpha1-syntrophin mediated by PDZ domains. Cell 84:757-767 (Pubitemid 26094205)
15. Bushby K, Finkel R, Birnkrant DJ, Case LE, Clemens PR, Cripe L, Kaul A, Kinnett K, McDonald C, Pandya S, Poysky J, Shapiro F, Tomezsko J, Constantin C, DMD Care Considerations Working Group (2009) Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and pharmacological and psychosocial management. Lancet Neurol 9:77-93
16. Chamberlain JS, Metzger J, Reyes M, Townsend D, Faulkner JA (2007) Dystrophin-deficient mdx mice display a reduced life span and are susceptible to spontaneous rhabdomyosarcoma. FASEB J 21:2195-2204 (Pubitemid 47026454)
17. Chang WJ, Iannaccone ST, Lau KS, Masters BS, McCabe TJ, McMillan K, Padre RC, Spencer MJ, Tidball JG, Stull JT (1996) Neuronal nitric oxide synthase and dystrophin-deficient muscular dystrophy. Proc Natl Acad Sci USA 93:9142-9147 (Pubitemid 26282032)
18. Chao DS, Gorospe JR, Brenman JE, Rafael JA, Peters MF, Froehner SC, Hoffman EP, Chamberlain JS, Bredt DS (1996) Selective loss of sarcolemmal nitric oxide synthase in Becker muscular dystrophy. J Exp Med 184:609-618 (Pubitemid 26324114)
19. Chao DS, Silvagno F, Xia H, Cornwell TL, Lincoln TM, Bredt DS (1997) Nitric oxide synthase and cyclic GMP-dependent protein kinase concentrated at the neuromuscular endplate. Neuroscience 76:665-672 (Pubitemid 27013408)
20. Chenard AA, Becane HM, Tertrain F, de Kermadec JM, Weiss YA (1993) Ventricular arrhythmia in Duchenne muscular dystrophy: prevalence, significance and prognosis. Neuromuscul Disord 3:201-206 (Pubitemid 23250404)
21. Chu V, Otero JM, Lopez O, Sullivan MF, Morgan JP, Amende I, Hampton TG (2002) Electrocardiographic findings in mdx mice: a cardiac phenotype of Duchenne muscular dystrophy. Muscle Nerve 26:513-519
22. Colussi C, Mozzetta C, Gurtner A, Illi B, Rosati J, Straino S, Ragone G, Pescatori M, Zaccagnini G, Antonini A, Minetti G, Martelli F, Piaggio G, Gallinari P, Steinkuhler C, Clementi E, DellAversana C, Altucci L, Mai A, Capogrossi MC, Puri PL, Gaetano C (2008) HDAC2 blockade by nitric oxide and histone deacetylase inhibitors reveals a common target in Duchenne muscular dystrophy treatment. Proc Natl Acad Sci USA 105:19183-19187
23. Craven KB, Zagotta WN (2006) CNG and HCN channels: two peas, one pod. Annu Rev Physiol 68:375-401
24. Crosbie RH, Barresi R, Campbell KP (2002) Loss of sarcolemma nNOS in sarcoglycan-deficient muscle. FASEB J 16:1786-1791 (Pubitemid 35340359)
25. Danialou G, Comtois AS, Dudley R, Karpati G, Vincent G, Des Rosiers C, Petrof BJ (2001) Dystrophin-deficient cardiomyocytes are abnormally vulnerable to mechanical stress-induced contractile failure and injury. FASEB J 15:1655-1667
26. Das A, Xi L, Kukreja RC (2008) Protein kinase G-dependent cardioprotective mechanism of phosphodiesterase-5 inhibition involves phosphorylation of ERK and GSK3beta. J Biol Chem 283:29572-29585
27. Davies KE, Nowak KJ (2006) Molecular mechanisms of muscular dystrophies: old and new players. Nat Rev Mol Cell Biol 7:762-773 (Pubitemid 44450460)
28. de Kermadec JM, Bécane HM, Chénard A, Tertrain F, Weiss Y (1994) Prevalence of left ventricular systolic dysfunction in Duchenne muscular dystrophy: an echocardiographic study. Am Heart J 127:618-623 (Pubitemid 24124693)
29. Dellorusso C, Crawford RW, Chamberlain JS, Brooks SV (2001) Tibialis anterior muscles in mdx mice are highly susceptible to contraction-induced injury. J Muscle Res Cell Motil 22:467-475 (Pubitemid 34264077)
30. Eagle M, Bourke J, Bullock R, Gibson M, Mehta J, Giddings D, Straub V, Bushby K (2007) Managing Duchenne muscular dystrophy-the additive effect of spinal surgery and home nocturnal ventilation in improving survival. Neuromuscul Disord 17:470-475 (Pubitemid 46795560)
31. Ervasti JM (2007) Dystrophin, its interactions with other proteins, and implications for muscular dystrophy. Biochim Biophys Acta 1772:108-117 (Pubitemid 46123911)
32. Ervasti JM, Campbell KP (1993) Dystrophin and the membrane skeleton. Curr Opin Cell Biol 5:82-87
33. Eu JP, Sun J, Xu L, Stamler JS, Meissner G (2000) The skeletal muscle calcium release channel: coupled O2 sensor and NO signaling functions. Cell 102:499-509
34. Fernhoff NB, Derbyshire ER, Marletta MA (2009) A nitric oxide/cysteine interaction mediates the activation of soluble guanylate cyclase. Proc Natl Acad Sci USA 106:21602-21607
35. Finsterer J, Stollberger C (2003) The heart in human dystrophinopathies. Cardiology 99:1-19 (Pubitemid 36206630)
36. Firestein BL, Bredt DS (1999) Interaction of neuronal nitric-oxide synthase and phosphofructokinase-M. J Biol Chem 274:10545-10550
37. Frankel KA, Rosser RJ (1976) The pathology of the heart in progressive muscular dystrophy: epimyocardial fibrosis. Hum Pathol 7:375-386
38. Hillier BJ, Christopherson KS, Prehoda KE, Bredt DS, Lim WA (1999) Unexpected modes of PDZ domain scaffolding revealed by structure of nNOS-syntrophin complex. Science 284:812-815 (Pubitemid 29291348)
39. Hoffman EP, Brown RH Jr, Kunkel LM (1987) Dystrophin: the protein product of the Duchenne muscular dystrophy locus. Cell 51:919-928
40. Hofmann F, Bernhard D, Lukowski R, Weinmeister P (2009) cGMP regulated protein kinases (cGK). Handb Exp Pharmacol 191:137-162
41. Ishikawa Y, Bach JR, Minami R (1999) Cardioprotection for Duchennes muscular dystrophy. Am Heart J 137:895-902
42. Ito K, Kimura S, Ozasa S, Matsukura M, Ikezawa M, Yoshioka K, Ueno H, Suzuki M, Araki K, Yamamura K, Miwa T, Dickson G, Thomas GD, Miike T (2006) Smooth muscle-specific dystrophin expression improves aberrant vasoregulation in mdx mice. Hum Mol Genet 15:2266-2275 (Pubitemid 43985517)
43. Jerusalem F, Engel AG, Gomez MR (1974) Duchenne dystrophy I. morphometric study of the muscle microvasculature. Brain 97:115-122
44. Kameya S, Miyagoe Y, Nonaka I, Ikemoto T, Endo M, Hanaoka K, Nabeshima Y, Takeda S (1999) alpha1-syntrophin gene disruption results in the absence of neuronal-type nitric-oxide synthase at the sarcolemma but does not induce muscle degeneration. J Biol Chem 274:2193-2200
45. Khairallah M, Khairallah R, Young ME, Dyck JR, Petrof BJ, Des Rosiers C (2007) Metabolic and signaling alterations in dystrophin-deficient hearts precede overt cardiomyopathy. J Mol Cell Cardiol 43:119-1129
46. Khairallah M, Khairallah RJ, Young ME, Allen BG, Gillis MA, Danialou G, Deschepper CF, Petrof BJ, Des Rosiers C (2008) Sildenafil and cardiomyocyte-specific cGMP signaling prevent cardiomyopathic changes associated with dystrophin deficiency. Proc Natl Acad Sci USA 105:7028-7033 (Pubitemid 351754524)
47. Kobayashi YM, Rader EP, Crawford RW, Iyengar NK, Thedens DR, Faulkner JA, Parikh SV, Weiss RM, Chamberlain JS, Moore SA, Campbell KP (2008) Sarcolemma-localized nNOS is required to maintain activity after mild exercise. Nature 456:511-515 (Pubitemid 352759004)
48. Koenig M, Monaco AP, Kunkel LM (1988) The complete sequence of dystrophin predicts a rodshaped cytoskeletal protein. Cell 53:219-228
49. Lai Y, Thomas GD, Yue Y, Yang HT, Li D, Long C, Judge L, Bostick B, Chamberlain JS, Terjung RL, Duan D (2009) Dystrophins carrying spectrin-like repeats 16 and 17 anchor nNOS to the sarcolemma and enhance exercise performance in a mouse model of muscular dystrophy. J Clin Invest 119:624-635
50. Lukowski R, Rybalkin SD, Loga F, Leiss V, Beavo JA, Hofmann F (2010) Cardiac hypertrophy is not amplified by deletion of cGMP-dependent kinase-I in cardiomyocytes. Proc Natl Acad Sci USA 107:5646-5651
51. Manzur AY, Kuntzer T, Pike M, Swan A (2008) Glucocorticoid corticosteroids for Duchenne muscular dystrophy. Cochrane Database Syst Rev 1:CD003725
52. Markham LW, Michelfelder EC, Border WL, Khoury PR, Spicer RL, Wong BL, Benson DW, Cripe LH (2006) Abnormalities of diastolic function precede dilated ardiomyopathy associated with Duchenne muscular dystrophy. J Am Soc Echocardiogr 19:865-871 (Pubitemid 43977862)
53. McConell GK, Wadley GD (2008) Potential role of nitric oxide in contraction-stimulated glucose uptake and mitochondrial biogenesis in skeletal muscle. Clin Exp Pharmacol Physiol 35:1488-1492
54. McConell GK, Bradley SJ, Stephens TJ, Canny BJ, Kingwell BA, Lee-Young RS (2007) Skeletal muscle nNOS mu protein content is increased by exercise training in humans. Am J Physiol Regul Integr Comp Physiol 293:R821-R828 (Pubitemid 47205068)
55. Mendell JR, Engel WK, Derrer EC (1971) Duchenne muscular dystrophy: functional ischemia reproduces its characteristic lesions. Science 172:1143-1145
56. Mergia E, Koesling D, Friebe A (2009) Genetic mouse models of the NO receptor soluble guanylyl cyclases. Handb Exp Pharmacol 191:33-46
57. Moriuchi T, Kagawa N, Mukoyama M, Hizawa K (1993) Autopsy analyses of the muscular dystrophies Tokushima. J Exp Med 40:83-93
58. Nagayama T, Zhang M, Hsu S, Takimoto E, Kass DA (2008) Sustained soluble guanylate cyclase stimulation offsets nitric-oxide synthase inhibition to restore acute cardiac modulation by sildenafil. J Pharmacol Exp Ther 326:380-387
59. Percival JM, Adams ME, Froehner SC (2006) Syntrophin: a molecular adaptor conferring a signaling role to the dystrophin-associated protein complex. In: Winder SJ (ed) Molecular mechanisms of muscular dystrophies. Landes Bioscience, TX
60. Percival JM, Anderson KN, Gregorevic P, Chamberlain JS, Froehner SC (2008) Functional deficits in nNOSmu-deficient skeletal muscle: myopathy in nNOS knockout mice. PLoS ONE 3:e3387
61. Percival JM, Anderson KN, Huang PL, Adams ME, Froehner SC (2010) Golgi and sarcolemmal nNOS isozymes differentially regulate contraction-induced fatigue and vasoconstriction in exercising skeletal muscle. J Clin Invest 120:816-826
62. Petrof BJ, Shrager JB, Stedman HH, Kelly AM, Sweeney HL (1993) Dystrophin protects the sarcolemma from stresses developed during muscle contraction. Proc Natl Acad Sci USA 90:3710-3714 (Pubitemid 23111437)
63. Quinlan JG, Hahn HS, Wong BL, Lorenz JN, Wenisch AS, Levin LS (2004) Evolution of the mdx mouse cardiomyopathy: physiological and morphological findings. Neuromuscul Disord 14:491-496 (Pubitemid 39141704)
64. Reffelmann T, Kloner RA (2009) Phosphodiesterase 5 inhibitors: are they cardioprotective? Cardiovasc Res 83:204-12
65. Sander M, Chavoshan B, Harris SA, Iannaccone ST, Stull JT, Thomas GD, Victor RG (2000) Functional muscle ischemia in neuronal nitric oxide synthase-deficient skeletal muscle of children with Duchenne muscular dystrophy. Proc Natl Acad Sci USA 97:13818-13823
66. Saraiva RM, Minhas KM, Raju SV, Barouch LA, Pitz E, Schuleri KH, Vandegaer K, Li D, Hare JM (2005) Deficiency of neuronal nitric oxide synthase increases mortality and cardiac remodeling after myocardial infarction: role of nitroso-redox equilibrium. Circulation 112:3415-3422 (Pubitemid 43739556)
67. Sears CE, Bryant SM, Ashley EA, Lygate CA, Rakovic S, Wallis HL, Neubauer S, Terrar DA, Casadei B (2003) Cardiac neuronal nitric oxide synthase isoform regulates myocardial contraction and calcium handling. Circ Res 92:e52-e59
68. Seddon M, Melikian N, Dworakowski R, Shabeeh H, Jiang B, Byrne J, Casadei B, Chowienczyk P, Shah AM (2009) Effects of neuronal nitric oxide synthase on human coronary artery diameter and blood flow in vivo. Circulation 119:2656-2662
69. Senzaki H, Smith CJ, Juang GJ, Isoda T, Mayer SP, Ohler A, Paolocci N, Tomaselli GF, Hare JM, Kass DA (2001) Cardiac phosphodiesterase 5 (cGMP-specific) modulates beta-adrenergic signaling in vivo and is down-regulated in heart failure. FASEB J 15:1718-1726 (Pubitemid 32730219)
70. Silvagno F, Xia H, Bredt DS (1996) Neuronal nitric-oxide synthase-mu, an alternatively spliced isoform expressed in differentiated skeletal muscle. J Biol Chem 271:11204-11208
71. Spurney CF, Knoblach S, Pistilli EE, Nagaraju K, Martin GR, Hoffman EP (2008) Dystrophindeficient cardiomyopathy in mouse: expression of Nox4 and Lox are associated with fibrosis and altered functional parameters in the heart. Neuromuscul Disord 18:371-381
72. Stedman HH, Sweeney HL, Shrager JB, Maguire HC, Panettieri RA, Petrof B, Narusawa M, Leferovich JM, Sladky JT, Kelly AM (1991) The mdx mouse diaphragm reproduces the degenerative changes of Duchenne muscular dystrophy. Nature 352:536-359
73. Stuehr DJ, Santolini J, Wang ZQ, Wei CC, Adak S (2004) Update on mechanism and catalytic regulation in the NO synthases. J Biol Chem 279:36167-36170 (Pubitemid 39128949)
74. Suzuki N, Motohashi N, Uezumi A, Fukada S, Yoshimura T, Itoyama Y, Aoki M, Miyagoe-Suzuki Y, Takeda S (2007) NOproduction results in suspension-inducedmuscle atrophy through dislocation of neuronal NOS. J Clin Invest 117:2468-2476 (Pubitemid 47494348)
75. Takimoto E, Champion HC, Li M, Belardi D, Ren S, Rodriguez ER, Bedja D, Gabrielson KL, Wang Y, Kass DA (2005) Chronic inhibition of cyclic GMP phosphodiesterase 5A prevents and reverses cardiac hypertrophy. Nat Med 11:214-222 (Pubitemid 40321358)
76. Thomas GD, Victor RG (1998) Nitric oxide mediates contraction-induced attenuation of sympathetic vasoconstriction in rat skeletal muscle. J Physiol 506:817-826 (Pubitemid 28062103)
77. Thomas GD, Sander M, Lau KS, Huang PL, Stull JT, Victor RG (1998) Impaired metabolic modulation of alpha-adrenergic vasoconstriction in dystrophin-deficient skeletal muscle. Proc Natl Acad Sci USA 95:15090-15095 (Pubitemid 29003761)
78. Thomas GD, Shaul PW, Yuhanna IS, Froehner SC, Adams ME (2003) Vasomodulation by skeletal muscle-derived nitric oxide requires alpha-syntrophin-mediated sarcolemmal localization of neuronal nitric oxide synthase. Circ Res 92:554-560 (Pubitemid 36368669)
79. Thrush PT, Allen HD, Viollet L, Mendell JR (2009) Re-examination of the electrocardiogram in boys with Duchenne muscular dystrophy and correlation with its dilated cardiomyopathy. Am J Cardiol 103:262-265
80. Tidball JG, Wehling-Henricks M (2004) Expression of a NOS transgene in dystrophin-deficient muscle reduces muscle membrane damage without increasing the expression of membraneassociated cytoskeletal proteins. Mol Genet Metab 82:312-320 (Pubitemid 39078711)
81. Townsend D, Yasuda S, Li S, Chamberlain JS, Metzger JM (2008) Emergent dilated cardiomyopathy caused by targeted repair of dystrophic skeletal muscle. Mol Ther 16:832-835 (Pubitemid 351587091)
82. Vandebrouck C, Duport G, Cognard C, Raymond G (2001) Cationic channels in normal and dystrophic human myotubes. Neuromuscul Disord 11:72-79 (Pubitemid 32109218)
83. Vandeput F, Krall J, Ockaili R, Salloum FN, Florio V, Corbin JD, Francis SH, Kukreja RC, Movsesian MA (2009) cGMP-hydrolytic activity and its inhibition by sildenafil in normal and failing human and mouse myocardium. J Pharmacol Exp Ther 330:884-891
84. Wallis RM, Corbin JD, Francis SH, Ellis P (1999) Tissue distribution of phospho-diesterase families and the effects of sildenafil on tissue cyclic nucleotides, platelet function, and the contractile responses of trabeculae carneae and aortic rings in vitro. Am J Cardiol 83:3C-12C (Pubitemid 29122752)
85. Ward ME, Toporsian M, Scott JA, Teoh H, Govindaraju V, Quan A, Wener AD, Wang G, Bevan SC, Newton DC, Marsden PA (2005) Hypoxia induces a functionally significant and translationally efficient neuronal NO synthase mRNA variant. J Clin Invest 115:3128-3139 (Pubitemid 41567577)
86. Wehling M, Spencer MJ, Tidball JG (2001) A nitric oxide synthase transgene ameliorates muscular dystrophy in mdx mice. J Cell Biol 155:123-131 (Pubitemid 34286213)
87. Wehling-Henricks M, Jordan MC, Roos KP, Deng B, Tidball JG (2005) Cardiomyopathy in dystrophin-deficient hearts is prevented by expression of a neuronal nitric oxide synthase transgene in the myocardium. Hum Mol Genet 14:1921-1933 (Pubitemid 41418029)
88. Wehling-Henricks M, Oltmann M, Rinaldi C, Myung KH, Tidball JG (2009) Loss of positive allosteric interactions between neuronal nitric oxide synthase and phosphoructokinase contributes to defects in glycolysis and increased fatigability in muscular dystrophy. Hum Mol Genet 18:3439-3451
89. Whitehead NP, Streamer M, Lusambili LI, Sachs F, AllenDG(2006) Streptomycin reduces stretchinduced membrane permeability in muscles from mdx mice. Neuromuscul Disord 16:845-854 (Pubitemid 44855593)
90. Willmann R, Possekel S, Dubach-Powell J, Meier T, Ruegg MA (2009) Mammalian animal models for Duchenne muscular dystrophy. Neuromuscul Disord 19:241-249
91. Wu B, Moulton HM, Iversen PL, Jiang J, Li J, Li J, Spurney CF, Sali A, Guerron AD, Nagaraju K, Doran T, Lu P, Xiao X, Lu QL (2008) Effective rescue of dystrophin improves cardiac function in dystrophin-deficient mice by a modified morpholino oligomer. Proc Natl Acad Sci USA 105:14814-14819
92. Xu KY, Huso DL, Dawson TM, Bredt DS, Becker LC (1999) Nitric oxide synthase in cardiac sarcoplasmic reticulum. Proc Natl Acad Sci USA 96:657-662 (Pubitemid 29061264)
93. Zhang YH, Zhang MH, Sears CE, Emanuel K, Redwood C, El-Armouche A, Kranias EG, Casadei B (2008) Reduced phospholamban phosphorylation is associated with impaired relaxation in left ventricular myocytes from neuronal NO synthase-deficient mice. Circ Res 102:242-249 (Pubitemid 351651129)