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01-09-2015 | Original Contribution

NOS1 induces NADPH oxidases and impairs contraction kinetics in aged murine ventricular myocytes

Authors: Marten Villmow, Udo Klöckner, Christophe Heymes, Michael Gekle, Uwe Rueckschloss

Published in: Basic Research in Cardiology | Issue 5/2015

Abstract

Nitric oxide (NO) modulates calcium transients and contraction of cardiomyocytes. However, it is largely unknown whether NO contributes also to alterations in the contractile function of cardiomyocytes during aging. Therefore, we analyzed the putative role of nitric oxide synthases and NO for the age-related alterations of cardiomyocyte contraction. We used C57BL/6 mice, nitric oxide synthase 1 (NOS1)-deficient mice (NOS1^−/−) and mice with cardiomyocyte-specific NOS1-overexpression to analyze contractions, calcium transients (Indo-1 fluorescence), acto-myosin ATPase activity (malachite green assay), NADPH oxidase activity (lucigenin chemiluminescence) of isolated ventricular myocytes and cardiac gene expression (Western blots, qPCR). In C57BL/6 mice, cardiac expression of NOS1 was upregulated by aging. Since we found a negative regulation of NOS1 expression by cAMP in isolated cardiomyocytes, we suggest that reduced efficacy of β-adrenergic signaling that is evident in aged hearts promotes upregulation of NOS1. Shortening and relengthening of cardiomyocytes from aged C57BL/6 mice were decelerated, but were normalized by pharmacological inhibition of NOS1/NO. Cardiomyocytes from NOS1^−/− mice displayed no age-related changes in contraction, calcium transients or acto-myosin ATPase activity. Aging increased cardiac expression of NADPH oxidase subunits NOX2 and NOX4 in C57BL/6 mice, but not in NOS1^−/− mice. Similarly, cardiac expression of NOX2 and NOX4 was upregulated in a murine model with cardiomyocyte-specific overexpression of NOS1. We conclude that age-dependently upregulated NOS1, putatively via reduced efficacy of β-adrenergic signaling, induces NADPH oxidases. By increasing nitrosative and oxidative stress, both enzyme systems act synergistically to decelerate contraction of aged cardiomyocytes.

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Amour J, Loyer X, Le Guen M, Mabrouk N, David JS, Camors E, Carusio N, Vivien B, Andriantsitohaina R, Heymes C, Riou B (2007) Altered contractile response due to increased beta3-adrenoceptor stimulation in diabetic cardiomyopathy: the role of nitric oxide synthase 1-derived nitric oxide. Anesthesiology 107:452–460. doi:10.1097/01.anes.0000278909.40408.24 CrossRefPubMed

Ashley EA, Sears CE, Bryant SM, Watkins HC, Casadei B (2002) Cardiac nitric oxide synthase 1 regulates basal and beta-adrenergic contractility in murine ventricular myocytes. Circulation 105:3011–3016. doi:10.1161/01.CIR.0000019516.31040.2D CrossRefPubMed

Barouch LA, Harrison RW, Skaf MW, Rosas GO, Cappola TP, Kobeissi ZA, Hobai IA, Lemmon CA, Burnett AL, O’Rourke 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. doi:10.1038/416337a CrossRefPubMed

Bendall JK, Cave AC, Heymes C, Gall N, Shah AM (2002) Pivotal role of a gp91(phox)-containing NADPH oxidase in angiotensin II-induced cardiac hypertrophy in mice. Circulation 105:293–296CrossRefPubMed

Berlin I, Grimaldi A, Bosquet F, Puech AJ (1986) Decreased beta-adrenergic sensitivity in insulin-dependent diabetic subjects. J Clin Endocrinol Metab 63:262–265. doi:10.1210/jcem-63-1-262 CrossRefPubMed

Birenbaum A, Tesse A, Loyer X, Michelet P, Andriantsitohaina R, Heymes C, Riou B, Amour J (2008) Involvement of beta 3-adrenoceptor in altered beta-adrenergic response in senescent heart: role of nitric oxide synthase 1-derived nitric oxide. Anesthesiology 109:1045–1053. doi:10.1097/ALN.0b013e31818d7e5a CrossRefPubMed

Brodde OE, Zerkowski HR, Schranz D, Broede-Sitz A, Michel-Reher M, Schäfer-Beisenbusch E, Piotrowski JA, Oelert H (1995) Age-dependent changes in the beta-adrenoceptor-G-protein(s)-adenylyl cyclase system in human right atrium. J Cardiovasc Pharmacol 26:20–26CrossRefPubMed

Brunner F, Wölkart G (2003) Peroxynitrite-induced cardiac depression: role of myofilament desensitization and cGMP pathway. Cardiovasc Res 60:355–364. doi:10.1016/j.cardiores.2003.08.001 CrossRefPubMed

Buttrick P, Malhotra A, Factor S, Greenen D, Leinwand L, Scheuer J (1991) Effect of aging and hypertension on myosin biochemistry and gene expression in the rat heart. Circ Res 68:645–652. doi:10.1161/01.RES.68.3.645 CrossRefPubMed

10.

Carter GS, Karl DW (1982) Inorganic phosphate assay with malachite green: an improvement and evaluation. J Biochem Biophys Methods 7:7–13. doi:10.1016/0165-022X(82)90031-8 CrossRefPubMed

11.

Damy T, Ratajczak P, Robidel E, Bendall JK, Oliviero P, Boczkowski J, Ebrahimian T, Marotte F, Samuel JL, Heymes C (2003) Upregulation of cardiac nitric oxide synthase 1-derived nitric oxide after myocardial infarction in senescent rats. FASEB J 17:1934–1936. doi:10.1096/fj.02-1208fje PubMed

12.

Damy T, Ratajczak P, Shah AM, Camors E, Marty I, Hasenfuss G, Marotte F, Samuel JL, Heymes C (2004) Increased neuronal nitric oxide synthase-derived NO production in the failing human heart. Lancet 363:1365–1367. doi:10.1016/S0140-6736(04)16048-0 CrossRefPubMed

13.

Deeb RS, Nuriel T, Cheung C, Summers B, Lamon BD, Gross SS, Hajjar DP (2013) Characterization of a cellular denitrase activity that reverses nitration of cyclooxygenase. Am J Physiol Heart Circ Physiol 305:H687–H698. doi:10.1152/ajpheart.00876.2012 PubMedCentralCrossRefPubMed

14.

Dinçer UD, Bidasee KR, Güner S, Tay A, Ozçelikay AT, Altan VM (2001) The effect of diabetes on expression of beta1-, beta2-, and beta3-adrenoreceptors in rat hearts. Diabetes 50:455–461. doi:10.2337/diabetes.50.2.455 CrossRefPubMed

15.

Dobson JG Jr, Fray J, Leonard JL, Pratt RE (2003) Molecular mechanisms of reduced beta-adrenergic signaling in the aged heart as revealed by genomic profiling. Physiol Genomics 15:142–147. doi:10.1152/physiolgenomics.00076.2003 CrossRefPubMed

16.

Farrell SR, Howlett SE (2008) The age-related decrease in catecholamine sensitivity is mediated by beta(1)-adrenergic receptors linked to a decrease in adenylate cyclase activity in ventricular myocytes from male Fischer 344 rats. Mech Ageing Dev 129:735–744. doi:10.1016/j.mad.2008.09.017 CrossRefPubMed

17.

Fukui T, Yoshiyama M, Hanatani A, Omura T, Yoshikawa J, Abe Y (2001) Expression of p22-phox and gp91-phox, essential components of NADPH oxidase, increases after myocardial infarction. Biochem Biophys Res Commun 281:1200–1206. doi:10.1006/bbrc.2001.4493 CrossRefPubMed

18.

Görg B, Qvartskhava N, Voss P, Grune T, Häussinger D, Schliess F (2007) Reversible inhibition of mammalian glutamine synthetase by tyrosine nitration. FEBS Lett 581:84–90. doi:10.1016/j.febslet.2006.11.081 CrossRefPubMed

19.

Guo Z, Zhang R, Li J, Xu G (2012) Effect of telmisartan on the expression of adiponectin receptors and nicotinamide adenine dinucleotide phosphate oxidase in the heart and aorta in type 2 diabetic rats. Cardiovasc Diabetol 11:94. doi:10.1186/1475-2840-11-94 PubMedCentralCrossRefPubMed

20.

Hafstad AD, Nabeebaccus AA, Shah AM (2013) Novel aspects of ROS signalling in heart failure. Basic Res Cardiol 108:359. doi:10.1007/s00395-013-0359-8 CrossRefPubMed

21.

Halley CM, Houghtaling PL, Khalil MK, Thomas JD, Jaber WA (2011) Mortality rate in patients with diastolic dysfunction and normal systolic function. Arch Intern Med 171:1082–1087. doi:10.1001/archinternmed.2011.244 CrossRefPubMed

22.

Hay I, Rich J, Ferber P, Burkhoff D, Maurer MS (2005) Role of impaired myocardial relaxation in the production of elevated left ventricular filling pressure. Am J Physiol Heart Circ Physiol 288:H1203–H1208. doi:10.1152/ajpheart.00681.2004 CrossRefPubMed

23.

Heinzel FR, Gres P, Boengler K, Duschin A, Konietzka I, Rassaf T, Snedovskaya J, Meyer S, Skyschally A, Kelm M, Heusch G, Schulz R (2008) Inducible nitric oxide synthase expression and cardiomyocyte dysfunction during sustained moderate ischemia in pigs. Circ Res 103:1120–1127. doi:10.1161/CIRCRESAHA.108.186015 CrossRefPubMed

24.

Heusch P, Aker S, Boengler K, Deindl E, van de Sand A, Klein K, Rassaf T, Konietzka I, Sewell A, Menazza S, Canton M, Heusch G, Di Lisa F, Schulz R (2010) Increased inducible nitric oxide synthase and arginase II expression in heart failure: no net nitrite/nitrate production and protein S-nitrosylation. Am J Physiol Heart Circ Physiol 299:H446–H453. doi:10.1152/ajpheart.01034.2009 CrossRefPubMed

25.

Huie RE, Padmaja S (1993) The reaction of no with superoxide. Free Radic Res Commun 18:195–199CrossRefPubMed

26.

Huynh K, Kiriazis H, Du XJ, Love JE, Gray SP, Jandeleit-Dahm KA, McMullen JR, Ritchie RH (2013) Targeting the upregulation of reactive oxygen species subsequent to hyperglycemia prevents type 1 diabetic cardiomyopathy in mice. Free Radic Biol Med 60:307–317. doi:10.1016/j.freeradbiomed.2013.02.021 CrossRefPubMed

27.

Irie Y, Saeki M, Kamisaki Y, Martin E, Murad F (2003) Histone H1.2 is a substrate for denitrase, an activity that reduces nitrotyrosine immunoreactivity in proteins. Proc Natl Acad Sci USA 100:5634–5639. doi:10.1073/pnas.1131756100 PubMedCentralCrossRefPubMed

28.

Isenberg G, Borschke B, Rueckschloss U (2003) Ca²⁺ transients of cardiomyocytes from senescent mice peak late and decay slowly. Cell Calcium 34:271–280. doi:10.1016/S0143-4160(03)00121-0 CrossRefPubMed

29.

Jin CZ, Jang JH, Wang Y, Kim JG, Bae YM, Shi J, Che CR, Kim SJ, Zhang YH (2012) Neuronal nitric oxide synthase is up-regulated by angiotensin II and attenuates NADPH oxidase activity and facilitates relaxation in murine left ventricular myocytes. J Mol Cell Cardiol 52:1274–1281. doi:10.1016/j.yjmcc.2012.03.013 CrossRefPubMed

30.

Kamata K, Satoh T, Tanaka H, Shigenobu K (1997) Changes in electrophysiological and mechanical responses of the rat papillary muscle to alpha- and beta-agonist in streptozotocin-induced diabetes. Can J Physiol Pharmacol 75:781–788. doi:10.1139/y97-095 CrossRefPubMed

31.

Kamisaki Y, Wada K, Bian K, Balabanli B, Davis K, Martin E, Behbod F, Lee YC, Murad F (1998) An activity in rat tissues that modifies nitrotyrosine-containing proteins. Proc Natl Acad Sci USA 95:11584–11589. doi:10.1073/pnas.95.20.11584 PubMedCentralCrossRefPubMed

32.

Kamkin A, Kiseleva I, Isenberg G (2003) Ion selectivity of stretch-activated cation currents in mouse ventricular myocytes. Pflugers Arch 446:220–231. doi:10.1007/s00424-003-1018-y PubMed

33.

Khan SA, Skaf MW, Harrison RW, Lee K, Minhas KM, Kumar A, Fradley M, Shoukas AA, Berkowitz DE, Hare JM (2003) Nitric oxide regulation of myocardial contractility and calcium cycling: independent impact of neuronal and endothelial nitric oxide synthases. Circ Res 92:1322–1329. doi:10.1161/01.RES.0000078171.52542.9E CrossRefPubMed

34.

Khan SA, Lee K, Minhas KM, Gonzalez DR, Raju SV, Tejani AD, Li D, Berkowitz DE, Hare JM (2004) Neuronal nitric oxide synthase negatively regulates xanthine oxidoreductase inhibition of cardiac excitation-contraction coupling. Proc Natl Acad Sci USA 101:15944–15948. doi:10.1073/pnas.0404136101 PubMedCentralCrossRefPubMed

35.

Kinugawa S, Huang H, Wang Z, Kaminski PM, Wolin MS, Hintze TH (2005) A defect of neuronal nitric oxide synthase increases xanthine oxidase-derived superoxide anion and attenuates the control of myocardial oxygen consumption by nitric oxide derived from endothelial nitric oxide synthase. Circ Res 96:355–362. doi:10.1161/01.RES.0000155331.09458.A7 CrossRefPubMed

36.

Knyushko TV, Sharov VS, Williams TD, Schöneich C, Bigelow DJ (2005) 3-Nitrotyrosine modification of SERCA2a in the aging heart: a distinct signature of the cellular redox environment. Biochemistry 44:13071–13081. doi:10.1021/bi051226n CrossRefPubMed

37.

Kohr MJ, Wang H, Wheeler DG, Velayutham M, Zweier JL, Ziolo MT (2008) Targeting of phospholamban by peroxynitrite decreases beta-adrenergic stimulation in cardiomyocytes. Cardiovasc Res 77:353–361. doi:10.1093/cvr/cvm018 PubMedCentralCrossRefPubMed

38.

Krijnen PA, Meischl C, Hack CE, Meijer CJ, Visser CA, Roos D, Niessen HW (2003) Increased Nox2 expression in human cardiomyocytes after acute myocardial infarction. J Clin Pathol 56:194–199. doi:10.1136/jcp.56.3.194 PubMedCentralCrossRefPubMed

39.

Kuo WN, Kanadia RN, Shanbhag VP, Toro R (1999) Denitration of peroxynitrite-treated proteins by ‘protein nitratases’ from rat brain and heart. Mol Cell Biochem 201:11–16. doi:10.1023/A:1007024126947 CrossRefPubMed

40.

Kuroda J, Ago T, Matsushima S, Zhai P, Schneider MD, Sadoshima J (2010) NADPH oxidase 4 (Nox4) is a major source of oxidative stress in the failing heart. Proc Natl Acad Sci USA 107:15565–15570. doi:10.1073/pnas.1002178107 PubMedCentralCrossRefPubMed

41.

Lakatta EG, Sollott SJ (2002) Perspectives on mammalian cardiovascular aging: humans to molecules. Comp Biochem Physiol, Part A Mol Integr Physiol 132:699–721. doi:10.1016/S1095-6433(02)00124-1 CrossRefPubMed

42.

Le Douairon Lahaye S, Rebillard A, Zguira MS, Malardé L, Saïag B, Gratas-Delamarche A, Carré F, Bekono FR (2011) Effects of exercise training combined with insulin treatment on cardiac NOS1 signaling pathways in type 1 diabetic rats. Mol Cell Biochem 347:53–62. doi:10.1007/s11010-010-0611-6 CrossRef

43.

Li JM, Gall NP, Grieve DJ, Chen M, Shah AM (2002) Activation of NADPH oxidase during progression of cardiac hypertrophy to failure. Hypertension 40:477–484. doi:10.1161/01.HYP.0000032031.30374.32 CrossRefPubMed

44.

Li Q, Wu S, Li SY, Lopez FL, Du M, Kajstura J, Anversa P, Ren J (2007) Cardiac-specific overexpression of insulin-like growth factor 1 attenuates aging-associated cardiac diastolic contractile dysfunction and protein damage. Am J Physiol Heart Circ Physiol 292:H1398–H1403. doi:10.1152/ajpheart.01036.2006 CrossRefPubMed

45.

Limouze J, Straight AF, Mitchison T, Sellers JR (2004) Specificity of blebbistatin, an inhibitor of myosin II. J Muscle Res Cell Motil 25:337–341. doi:10.1007/s10974-004-6060-7 CrossRefPubMed

46.

Lokuta AJ, Maertz NA, Meethal SV, Potter KT, Kamp TJ, Valdivia HH, Haworth RA (2005) Increased nitration of sarcoplasmic reticulum Ca2+ -ATPase in human heart failure. Circulation 111:988–995. doi:10.1161/01.CIR.0000156461.81529.D7 CrossRefPubMed

47.

Lompre AM, Lambert F, Lakatta EG, Schwartz K (1991) Expression of sarcoplasmic reticulum Ca(2+)-ATPase and calsequestrin genes in rat heart during ontogenic development and aging. Circ Res 69:1380–1388. doi:10.1161/01.RES.69.5.1380 CrossRefPubMed

48.

Loyer X, Gómez AM, Milliez P, Fernandez-Velasco M, Vangheluwe P, Vinet L, Charue D, Vaudin E, Zhang W, Sainte-Marie Y, Robidel E, Marty I, Mayer B, Jaisser F, Mercadier JJ, Richard S, Shah AM, Bénitah JP, Samuel JL, Heymes C (2008) Cardiomyocyte overexpression of neuronal nitric oxide synthase delays transition toward heart failure in response to pressure overload by preserving calcium cycling. Circulation 117:3187–3198. doi:10.1161/CIRCULATIONAHA.107.741702 CrossRefPubMed

49.

Malan D, Levi RC, Alloatti G, Marcantoni A, Bedendi I, Gallo MP (2003) Cyclic AMP and cyclic GMP independent stimulation of ventricular calcium current by peroxynitrite donors in guinea pig myocytes. J Cell Physiol 197:284–296. doi:10.1002/jcp.10368 CrossRefPubMed

50.

McGrady M, Reid CM, Shiel L, Wolfe R, Boffa U, Liew D, Campbell DJ, Prior D, Krum H (2013) N-terminal B-type natriuretic peptide and the association with left ventricular diastolic function in a population at high risk of incident heart failure: results of the SCReening Evaluation of the Evolution of New-Heart Failure Study (SCREEN-HF). Eur J Heart Fail 15:573–580. doi:10.1093/eurjhf/hft001 CrossRefPubMed

51.

Moniotte S, Kobzik L, Feron O, Trochu JN, Gauthier C, Balligand JL (2001) Upregulation of beta(3)-adrenoceptors and altered contractile response to inotropic amines in human failing myocardium. Circulation 103:1649–1655. doi:10.1161/01.CIR.103.12.1649 CrossRefPubMed

52.

Murdoch CE, Zhang M, Cave AC, Shah AM (2006) NADPH oxidase-dependent redox signalling in cardiac hypertrophy, remodelling and failure. Cardiovasc Res 71:208–215CrossRefPubMed

53.

Muzaffar S, Shukla N, Angelini G, Jeremy JY (2004) Nitroaspirins and morpholinosydnonimine but not aspirin inhibit the formation of superoxide and the expression of gp91phox induced by endotoxin and cytokines in pig pulmonary artery vascular smooth muscle cells and endothelial cells. Circulation 110:1140–1147. doi:10.1161/01.CIR.0000139851.50067.E4 CrossRefPubMed

54.

Olukman M, Orhan CE, Celenk FG, Ulker S (2010) Apocynin restores endothelial dysfunction in streptozotocin diabetic rats through regulation of nitric oxide synthase and NADPH oxidase expressions. J Diabetes Complications 24:415–423. doi:10.1016/j.jdiacomp.2010.02.001 CrossRefPubMed

55.

Pi Y, Zhang D, Kemnitz KR, Wang H, Walker JW (2003) Protein kinase C and A sites on troponin I regulate myofilament Ca2+ sensitivity and ATPase activity in the mouse myocardium. J Physiol 552:845–857. doi:10.1113/jphysiol.2003.045260 PubMedCentralCrossRefPubMed

56.

Post H, Schulz R, Gres P, Heusch G (2001) No involvement of nitric oxide in the limitation of beta-adrenergic inotropic responsiveness during ischemia. Am J Physiol Heart Circ Physiol 281:H2392–H2397PubMed

57.

Rueckschloss U, Quinn MT, Holtz J, Morawietz H (2002) Dose-dependent regulation of NAD(P)H oxidase expression by angiotensin II in human endothelial cells: protective effect of angiotensin II type 1 receptor blockade in patients with coronary artery disease. Arterioscler Thromb Vasc Biol 22:1845–1851CrossRefPubMed

58.

Rueckschloss U, Villmow M, Klöckner U (2010) NADPH oxidase-derived superoxide impairs calcium transients and contraction in aged murine ventricular myocytes. Exp Gerontol 45:788–796. doi:10.1016/j.exger.2010.05.002 CrossRefPubMed

59.

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. doi:10.1161/01.RES.0000064585.95749.6D CrossRefPubMed

60.

Sears CE, Ashley EA, Casadei B (2004) Nitric oxide control of cardiac function: is neuronal nitric oxide synthase a key component? Philos Trans R Soc Lond B Biol Sci 359:1021–1044. doi:10.1098/rstb.2004.1477 PubMedCentralCrossRefPubMed

61.

Shi Q, Xu H, Yu H, Zhang N, Ye Y, Estevez AG, Deng H, Gibson GE (2011) Inactivation and reactivation of the mitochondrial α-ketoglutarate dehydrogenase complex. J Biol Chem 286:17640–17648. doi:10.1074/jbc.M110.203018 PubMedCentralCrossRefPubMed

62.

Silberman GA, Fan TH, Liu H, Jiao Z, Xiao HD, Lovelock JD, Boulden BM, Widder J, Fredd S, Bernstein KE, Wolska BM, Dikalov S, Harrison DG, Dudley SC Jr (2010) Uncoupled cardiac nitric oxide synthase mediates diastolic dysfunction. Circulation 121:519–528. doi:10.1161/CIRCULATIONAHA.109.883777 PubMedCentralCrossRefPubMed

63.

Snook JH, Li J, Helmke BP, Guilford WH (2008) Peroxynitrite inhibits myofibrillar protein function in an in vitro assay of motility. Free Radic Biol Med 44:14–23. doi:10.1016/j.freeradbiomed.2007.09.004 PubMedCentralCrossRefPubMed

64.

Swartz DR, Zhang D, Yancey KW (1999) Cross bridge-dependent activation of contraction in cardiac myofibrils at low pH. Am J Physiol 276:H1460–H1467PubMed

65.

Takimoto E, Champion HC, Li M, Ren S, Rodriguez ER, Tavazzi B, Lazzarino G, Paolocci N, Gabrielson KL, Wang Y, Kass DA (2005) Oxidant stress from nitric oxide synthase-3 uncoupling stimulates cardiac pathologic remodeling from chronic pressure load. J Clin Invest 115:1221–1231. doi:10.1172/JCI21968 PubMedCentralCrossRefPubMed

66.

Takimoto Y, Aoyama T, Keyamura R, Shinoda E, Hattori R, Yui Y, Sasayama S (2000) Differential expression of three types of nitric oxide synthase in both infarcted and non-infarcted left ventricles after myocardial infarction in the rat. Int J Cardiol 76:135–145. doi:10.1016/S0167-5273(00)00394-6 CrossRefPubMed

67.

Tobise K, Ishikawa Y, Holmer SR, Im MJ, Newell JB, Yoshie H, Fujita M, Susannie EE, Homcy CJ (1994) Changes in type VI adenylyl cyclase isoform expression correlate with a decreased capacity for cAMP generation in the aging ventricle. Circ Res 74:596–603. doi:10.1161/01.RES.74.4.596 CrossRefPubMed

68.

Touyz RM, Chen X, Tabet F, Yao G, He G, Quinn MT, Pagano PJ, Schiffrin EL (2002) Expression of a functionally active gp91phox-containing neutrophil-type NAD(P)H oxidase in smooth muscle cells from human resistance arteries: regulation by angiotensin II. Circ Res 90:1205–1213CrossRefPubMed

69.

Viner RI, Huhmer AF, Bigelow DJ, Schoneich C (1996) The oxidative inactivation of sarcoplasmic reticulum Ca(2+)-ATPase by peroxynitrite. Free Radic Res 24:243–259. doi:10.3109/10715769609088022 CrossRefPubMed

70.

Wang H, Kohr MJ, Traynham CJ, Wheeler DG, Janssen PM, Ziolo MT (2008) Neuronal nitric oxide synthase signaling within cardiac myocytes targets phospholamban. Am J Physiol Cell Physiol 294:C1566–C1575. doi:10.1152/ajpcell.00367.2007 PubMedCentralCrossRefPubMed

71.

Wang H, Viatchenko-Karpinski S, Sun J, Györke I, Benkusky NA, Kohr MJ, Valdivia HH, Murphy E, Györke S, Ziolo MT (2010) Regulation of myocyte contraction via neuronal nitric oxide synthase: role of ryanodine receptor S-nitrosylation. J Physiol 588:2905–2917. doi:10.1113/jphysiol.2010.192617 PubMedCentralCrossRefPubMed

72.

Wichelhaus A, Russ M, Petersen S, Eckel J (1994) G protein expression and adenylate cyclase regulation in ventricular cardiomyocytes from STZ-diabetic rats. Am J Physiol 267:H548–H555PubMed

73.

Xiao RP, Tomhave ED, Wang DJ, Ji X, Boluyt MO, Cheng H, Lakatta EG, Koch WJ (1998) Age-associated reductions in cardiac beta1- and beta2-adrenergic responses without changes in inhibitory G proteins or receptor kinases. J Clin Invest 101:1273–1282. doi:10.1172/JCI1335 PubMedCentralCrossRefPubMed

74.

Ye J, Coulouris G, Zaretskaya I, Cutcutache I, Rozen S, Madden TL (2012) Primer-BLAST: a tool to design target-specific primers for polymerase chain reaction. BMC Bioinformatics 13:134. doi:10.1186/1471-2105-13-134 PubMedCentralCrossRefPubMed

75.

Zhang YH, Casadei B (2012) Sub-cellular targeting of constitutive NOS in health and disease. J Mol Cell Cardiol 52:341–350. doi:10.1016/j.yjmcc.2011.09.006 CrossRefPubMed

76.

Zhang ZS, Cheng HJ, Onishi K, Ohte N, Wannenburg T, Cheng CP (2005) Enhanced inhibition of L-type Ca2+ current by beta3-adrenergic stimulation in failing rat heart. J Pharmacol Exp Ther 315:1203–1211. doi:10.1124/jpet.105.089672 CrossRefPubMed

Title: NOS1 induces NADPH oxidases and impairs contraction kinetics in aged murine ventricular myocytes
Authors: Marten Villmow
Udo Klöckner
Christophe Heymes
Michael Gekle
Uwe Rueckschloss
Publication date: 01-09-2015
Publisher: Springer Berlin Heidelberg
Published in: Basic Research in Cardiology / Issue 5/2015
Print ISSN: 0300-8428
Electronic ISSN: 1435-1803
DOI: https://doi.org/10.1007/s00395-015-0506-5

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