Skip to main content

Sympathetic Nervous System Signaling in Heart Failure and Cardiac Aging

  • Chapter
Pathophysiology and Pharmacotherapy of Cardiovascular Disease

Abstract

Heart failure represents the leading cause of death, especially among the elderly. Despite the development of numerous therapeutic strategies, heart failure prevalence is still increasing. Ergo, exploring the molecular mechanisms underlying aging-related heart failure seems to be of particular relevance. Intriguingly, the fields of cardiovascular disease and aging, which have remained largely separate hitherto, seem to have a common point in the sympathetic nervous system. Indeed, mounting evidence indicates that adrenergic receptors are functionally involved in numerous processes underlying both aging and cardiovascular disease. This chapter will review the pathophysiological role of the sympathetic nervous system in heart failure and cardiac aging.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Santulli G. Epidemiology of cardiovascular disease in the 21st century: updated numbers and updated facts. J Cardiovasc Dis (JCvD). 2013;1(1):1–2.

    Google Scholar 

  2. Rosca MG, Hoppel CL. Mitochondria in heart failure. Cardiovasc Res. 2010;88(1):40–50. PubMed PMID: 20668004. Pubmed Central PMCID: 3025720.

    PubMed Central  CAS  PubMed  Google Scholar 

  3. Santulli G, Ciccarelli M, Trimarco B, Iaccarino G. Physical activity ameliorates cardiovascular health in elderly subjects: the functional role of the beta adrenergic system. Front Physiol. 2013;4:209. PubMed PMID: 23964243. Pubmed Central PMCID: 3740240. Epub 2013/08/22. eng.

    PubMed Central  PubMed  Google Scholar 

  4. Czuriga D, Paulus WJ, Czuriga I, Edes I, Papp Z, Borbely A. Cellular mechanisms for diastolic dysfunction in the human heart. Curr Pharm Biotechnol. 2012;13(13):2532–8. PubMed PMID: 22280428.

    CAS  PubMed  Google Scholar 

  5. Rahman F, Kwan GF, Benjamin EJ. Global epidemiology of atrial fibrillation. Nat Rev Cardiol. 2014;11:639–54. PubMed PMID: 25113750.

    Google Scholar 

  6. D’Ascia SL, D’Ascia C, Marino V, Lombardi A, Santulli R, Chiariello M, et al. Cardiac resynchronisation therapy response predicts occurrence of atrial fibrillation in non-ischaemic dilated cardiomyopathy. Int J Clin Pract. 2011;65(11):1149–55. PubMed PMID: 21995693. Epub 2011/10/15. eng.

    PubMed  Google Scholar 

  7. Santulli G, D’Ascia SL, D’Ascia C. Development of atrial fibrillation in recipients of cardiac resynchronization therapy: the role of atrial reverse remodelling. Can J Cardiol. 2012;28(2):245, author reply e17–8. PubMed PMID: 22244772. Epub 2012/01/17. eng.

    PubMed  Google Scholar 

  8. Lanni F, Santulli G, Izzo R, Rubattu S, Zanda B, Volpe M, et al. The Pl(A1/A2) polymorphism of glycoprotein IIIa and cerebrovascular events in hypertension: increased risk of ischemic stroke in high-risk patients. J Hypertens. 2007;25(3):551–6. PubMed PMID: 17278970.

    CAS  PubMed  Google Scholar 

  9. Sorriento D, Santulli G, Fusco A, Anastasio A, Trimarco B, Iaccarino G. Intracardiac injection of AdGRK5-NT reduces left ventricular hypertrophy by inhibiting NF-kappaB-dependent hypertrophic gene expression. Hypertension. 2010;56(4):696–704. PubMed PMID: 20660817. Epub 2010/07/28. eng.

    CAS  PubMed  Google Scholar 

  10. Hees PS, Fleg JL, Lakatta EG, Shapiro EP. Left ventricular remodeling with age in normal men versus women: novel insights using three-dimensional magnetic resonance imaging. Am J Cardiol. 2002;90(11):1231–6. PubMed PMID: 12450604.

    PubMed  Google Scholar 

  11. Gorelick PB, Scuteri A, Black SE, Decarli C, Greenberg SM, Iadecola C, et al. Vascular contributions to cognitive impairment and dementia: a statement for healthcare professionals from the american heart association/american stroke association. Stroke J Cereb Circ. 2011;42(9):2672–713. PubMed PMID: 21778438. Pubmed Central PMCID: 3778669.

    Google Scholar 

  12. Cantini C, Kieffer P, Corman B, Liminana P, Atkinson J, Lartaud-Idjouadiene I. Aminoguanidine and aortic wall mechanics, structure, and composition in aged rats. Hypertension. 2001;38(4):943–8. PubMed PMID: 11641314. Epub 2001/10/20. eng.

    CAS  PubMed  Google Scholar 

  13. Sonkusare SK, Bonev AD, Ledoux J, Liedtke W, Kotlikoff MI, Heppner TJ, et al. Elementary Ca2+ signals through endothelial TRPV4 channels regulate vascular function. Science. 2012;336(6081):597–601. PubMed PMID: 22556255. Pubmed Central PMCID: 3715993. Epub 2012/05/05. eng.

    PubMed Central  CAS  PubMed  Google Scholar 

  14. Santulli G, Wronska A, Kunihiro U, Diacovo T, Gao M, Marx S, et al. A selective microRNA-based strategy inhibits restenosis while preserving endothelial function. J Clin Invest. 2014;124:4102–14. eng.

    PubMed Central  CAS  PubMed  Google Scholar 

  15. Santulli G, Cipolletta E, Sorriento D, Del Giudice C, Anastasio A, Monaco S, et al. CaMK4 gene deletion induces hypertension. J Am Heart Assoc. 2012;1(4):e001081. PubMed PMID: 23130158. Pubmed Central PMCID: 3487344. Epub 2012/11/07. eng.

    PubMed Central  PubMed  Google Scholar 

  16. Iaccarino G, Ciccarelli M, Sorriento D, Cipolletta E, Cerullo V, Iovino GL, et al. AKT participates in endothelial dysfunction in hypertension. Circulation. 2004;109(21):2587–93. PubMed PMID: 15136501.

    CAS  PubMed  Google Scholar 

  17. Santulli G, Lombardi A, Sorriento D, Anastasio A, Del Giudice C, Formisano P, et al. Age-related impairment in insulin release: the essential role of beta(2)-adrenergic receptor. Diabetes. 2012;61(3):692–701. PubMed PMID: 22315324. Pubmed Central PMCID: 3282797.

    PubMed Central  CAS  PubMed  Google Scholar 

  18. Ciccarelli M, Rusciano MR, Sorriento D, Basilicata F, Santulli G, Campiglia P, et al. CaMKII protects MKP-1 from proteasome degradation in endothelial cells. Cell Signal. 2014;26:2167–74. PubMed PMID: 25007998.

    CAS  PubMed  Google Scholar 

  19. Kasai RS, Kusumi A. Single-molecule imaging revealed dynamic GPCR dimerization. Curr Opin Cell Biol. 2014;27:78–86. PubMed PMID: 24480089.

    CAS  PubMed  Google Scholar 

  20. Santulli G, Trimarco B, Iaccarino G. G-protein-coupled receptor kinase 2 and hypertension: molecular insights and pathophysiological mechanisms. High Blood Press Cardiovasc Prev Off J Ital Soc Hypertens. 2013;20(1):5–12. PubMed PMID: 23532739.

    CAS  Google Scholar 

  21. Penela P, Ribas C, Mayor Jr F. Mechanisms of regulation of the expression and function of G protein-coupled receptor kinases. Cell Signal. 2003;15(11):973–81. PubMed PMID: 14499340.

    CAS  PubMed  Google Scholar 

  22. Iaccarino G, Barbato E, Cipolletta E, De Amicis V, Margulies KB, Leosco D, et al. Elevated myocardial and lymphocyte GRK2 expression and activity in human heart failure. Eur Heart J. 2005;26(17):1752–8. PubMed PMID: 16055494. Epub 2005/08/02. eng.

    CAS  PubMed  Google Scholar 

  23. Harris DM, Cohn HI, Pesant S, Eckhart AD. GPCR signalling in hypertension: role of GRKs. Clin Sci (Lond). 2008;115(3):79–89. PubMed PMID: 18593382. Epub 2008/07/03. eng.

    CAS  Google Scholar 

  24. Mei Y, Yin N, Jin X, He J, Yin Z. The regulatory role of the adrenergic agonists phenylephrine and isoproterenol on fetal hemoglobin expression and erythroid differentiation. Endocrinology. 2013;154(12):4640–9. PubMed PMID: 24080366.

    CAS  PubMed  Google Scholar 

  25. Lampri E, Ioachim E. Angiogenesis: something old, something new. In: Santulli G, editor. Angiogenesis: insight from a systematic overview. New York: Nova Science Publishers; 2013. p. 1–30.

    Google Scholar 

  26. O’Connell TD, Jensen BC, Baker AJ, Simpson PC. Cardiac alpha1-adrenergic receptors: novel aspects of expression, signaling mechanisms, physiologic function, and clinical importance. Pharmacol Rev. 2014;66(1):308–33. PubMed PMID: 24368739. Pubmed Central PMCID: 3880467.

    PubMed Central  PubMed  Google Scholar 

  27. Ruuskanen JO, Laurila J, Xhaard H, Rantanen VV, Vuoriluoto K, Wurster S, et al. Conserved structural, pharmacological and functional properties among the three human and five zebrafish alpha 2-adrenoceptors. Br J Pharmacol. 2005;144(2):165–77. PubMed PMID: 15655522. Pubmed Central PMCID: 1575993.

    PubMed Central  CAS  PubMed  Google Scholar 

  28. Vicco MH, Pujato N, Bontempi I, Rodeles L, Marcipar I, Bottasso OA. beta1-selective adrenoceptor antagonists increase plasma levels of anti-p2beta antibodies and decrease cardiac involvement in chronic progressive Chagas heart disease. Can J Cardiol. 2014;30(3):332–7. PubMed PMID: 24370375.

    PubMed  Google Scholar 

  29. Santulli G, Iaccarino G. Pinpointing beta adrenergic receptor in ageing pathophysiology: victim or executioner? Evidence from crime scenes. Immun Ageing I A. 2013;10(1):10. PubMed PMID: 23497413. Pubmed Central PMCID: 3763845. Epub 2013/03/19. eng.

    Google Scholar 

  30. Belge C, Hammond J, Dubois-Deruy E, Manoury B, Hamelet J, Beauloye C, et al. Enhanced expression of beta3-adrenoceptors in cardiac myocytes attenuates neurohormone-induced hypertrophic remodeling through nitric oxide synthase. Circulation. 2014;129(4):451–62. PubMed PMID: 24190960.

    CAS  PubMed  Google Scholar 

  31. Xiao RP. Beta-adrenergic signaling in the heart: dual coupling of the beta2-adrenergic receptor to G(s) and G(i) proteins. Sci STKE Signal Transduct Knowl Environ. 2001;2001(104):re15. PubMed PMID: 11604549. Epub 2001/10/18. eng.

    CAS  Google Scholar 

  32. Sun Y, Huang J, Xiang Y, Bastepe M, Juppner H, Kobilka BK, et al. Dosage-dependent switch from G protein-coupled to G protein-independent signaling by a GPCR. EMBO J. 2007;26(1):53–64. PubMed PMID: 17170700. Pubmed Central PMCID: 1782364. Epub 2006/12/16. eng.

    PubMed Central  PubMed  Google Scholar 

  33. Kaya AI, Onaran HO, Ozcan G, Ambrosio C, Costa T, Balli S, et al. Cell contact-dependent functional selectivity of beta2-adrenergic receptor ligands in stimulating cAMP accumulation and extracellular signal-regulated kinase phosphorylation. J Biol Chem. 2012;287(9):6362–74. PubMed PMID: 22241475. Pubmed Central PMCID: 3307305. Epub 2012/01/14. eng.

    PubMed Central  CAS  PubMed  Google Scholar 

  34. Li H, Ma XQ, Ye F, Zhang J, Zhou X, Wang ZH, et al. Expressions of cardiac sympathetic norepinephrine transporter and beta1-adrenergic receptor decreased in aged rats. J Zhejiang Univ Sci B. 2009;10(3):203–10. PubMed PMID: 19283875. Pubmed Central PMCID: 2650030.

    PubMed Central  CAS  PubMed  Google Scholar 

  35. White M, Roden R, Minobe W, Khan MF, Larrabee P, Wollmering M, et al. Age-related changes in beta-adrenergic neuroeffector systems in the human heart. Circulation. 1994;90(3):1225–38. PubMed PMID: 8087932. Epub 1994/09/01. eng.

    CAS  PubMed  Google Scholar 

  36. Mika D, Richter W, Westenbroek RE, Catterall WA, Conti M. PDE4B mediates local feedback regulation of beta(1)-adrenergic cAMP signaling in a sarcolemmal compartment of cardiac myocytes. J Cell Sci. 2014;127(Pt 5):1033–42. PubMed PMID: 24413164. Pubmed Central PMCID: 3937773. Epub 2014/01/15. eng.

    PubMed Central  CAS  PubMed  Google Scholar 

  37. Bruzzone A, Sauliere A, Finana F, Senard JM, Luthy I, Gales C. Dosage-dependent regulation of cell proliferation and adhesion through dual beta2-adrenergic receptor/cAMP signals. FASEB J Off Publ Fed Am Soc Exp Biol. 2014;28(3):1342–54. PubMed PMID: 24308976. Epub 2013/12/07. eng.

    CAS  Google Scholar 

  38. Xie W, Santulli G, Guo X, Gao M, Chen BX, Marks AR. Imaging atrial arrhythmic intracellular calcium in intact heart. J Mol Cell Cardiol. 2013;64:120–3. PubMed PMID: 24041536. Epub 2013/09/18. eng.

    PubMed Central  CAS  PubMed  Google Scholar 

  39. Kirk JA, Holewinski RJ, Kooij V, Agnetti G, Tunin RS, Witayavanitkul N, et al. Cardiac resynchronization sensitizes the sarcomere to calcium by reactivating GSK-3beta. J Clin Invest. 2014;124(1):129–38. PubMed PMID: 24292707. Pubmed Central PMCID: 3871225.

    PubMed Central  CAS  PubMed  Google Scholar 

  40. Wright PT, Nikolaev VO, O’Hara T, Diakonov I, Bhargava A, Tokar S, et al. Caveolin-3 regulates compartmentation of cardiomyocyte beta2-adrenergic receptor-mediated cAMP signaling. J Mol Cell Cardiol. 2014;67:38–48. PubMed PMID: 24345421.

    PubMed Central  CAS  PubMed  Google Scholar 

  41. Santulli G. Adrenal signaling in heart failure: something more than a distant ship’s smoke on the horizon. Hypertension. 2014;63(2):215–6. PubMed PMID: 24218430.

    CAS  PubMed  Google Scholar 

  42. Izzo R, Cipolletta E, Ciccarelli M, Campanile A, Santulli G, Palumbo G, et al. Enhanced GRK2 expression and desensitization of betaAR vasodilatation in hypertensive patients. Clin Transl Sci. 2008;1(3):215–20. PubMed PMID: 20443852. Epub 2008/12/01. eng.

    CAS  PubMed  Google Scholar 

  43. Santulli G, Basilicata MF, De Simone M, Del Giudice C, Anastasio A, Sorriento D, et al. Evaluation of the anti-angiogenic properties of the new selective alphaVbeta3 integrin antagonist RGDechiHCit. J Transl Med. 2011;9:7. PubMed PMID: 21232121. Epub 2011/01/15. eng.

    PubMed Central  CAS  PubMed  Google Scholar 

  44. Sorriento D, Santulli G, Del Giudice C, Anastasio A, Trimarco B, Iaccarino G. Endothelial cells are able to synthesize and release catecholamines both in vitro and in vivo. Hypertension. 2012;60(1):129–36. PubMed PMID: 22665130.

    CAS  PubMed  Google Scholar 

  45. Iaccarino G, Ciccarelli M, Sorriento D, Galasso G, Campanile A, Santulli G, et al. Ischemic neoangiogenesis enhanced by beta2-adrenergic receptor overexpression: a novel role for the endothelial adrenergic system. Circ Res. 2005;97(11):1182–9. PubMed PMID: 16239589. Epub 2005/10/22. eng.

    CAS  PubMed  Google Scholar 

  46. Ritchie RH, Leo CH, Qin C, Stephenson EJ, Bowden MA, Buxton KD, et al. Low intrinsic exercise capacity in rats predisposes to age-dependent cardiac remodeling independent of macrovascular function. Am J Physiol Heart Circ Physiol. 2013;304(5):H729–39. PubMed PMID: 23262135. Pubmed Central PMCID: 3833993. Epub 2012/12/25. eng.

    PubMed Central  CAS  PubMed  Google Scholar 

  47. Santulli G. Coronary heart disease risk factors and mortality. JAMA J Am Med Assoc. 2012;307(11):1137. PubMed PMID: 22436947. author reply 8. Epub 2012/03/23. eng.

    CAS  Google Scholar 

  48. Vu TH, Stamler J, Liu K, McDermott MM, Lloyd-Jones DM, Pirzada A, et al. Prospective relationship of low cardiovascular risk factor profile at younger ages to ankle-brachial index: 39-year follow-up-the chicago healthy aging study. J Am Heart Assoc. 2012;1(6):e001545. PubMed PMID: 23316312. Pubmed Central PMCID: 3540658.

    PubMed Central  PubMed  Google Scholar 

  49. Sardu C, Marfella R, Santulli G. Impact of diabetes mellitus on the clinical response to cardiac resynchronization therapy in elderly people. J Cardiovasc Transl Res. 2014;7(3):362–8. PubMed PMID: 24500410. Epub 2014/02/07. eng.

    PubMed  Google Scholar 

  50. Begum N, Shen W, Manganiello V. Role of PDE3A in regulation of cell cycle progression in mouse vascular smooth muscle cells and oocytes: implications in cardiovascular diseases and infertility. Curr Opin Pharmacol. 2011;11(6):725–9. PubMed PMID: 22051884. Pubmed Central PMCID: 3225595.

    PubMed Central  CAS  PubMed  Google Scholar 

  51. Lavi S, Nevo O, Thaler I, Rosenfeld R, Dayan L, Hirshoren N, et al. Effect of aging on the cardiovascular regulatory systems in healthy women. Am J Physiol Regul Integr Comp Physiol. 2007;292(2):R788–93. PubMed PMID: 16946083.

    CAS  PubMed  Google Scholar 

  52. Menotti A, Lanti M, Mancini M, Zanchetti A, Laurenzi M, Terradura Vagnarelli O, et al. Moderate leisure time physical activity and occurrence of cardiovascular events: a 10-year follow-up in the Gubbio population study. J Cardiovasc Dis. 2014;2(5):218–24.

    Google Scholar 

  53. Heinonen I, Wendelin-Saarenhovi M, Kaskinoro K, Knuuti J, Scheinin M, Kalliokoski KK. Inhibition of alpha-adrenergic tone disturbs the distribution of blood flow in the exercising human limb. Am J Physiol Heart Circ Physiol. 2013;305(2):H163–72. PubMed PMID: 23666670.

    CAS  PubMed  Google Scholar 

  54. Wu L, Liu L. Systematic review and meta-analysis evaluating the impact of vitamin D on the risk of heart failure: new evidence from population-based studies. J Cardiovasc Dis. 2014;2(3):159–73.

    Google Scholar 

  55. Al Maluli H, DeStephan C. Hemodynamic monitoring in the intensive care unit. J Cardiovasc Dis. 2014;2(2):101–15.

    Google Scholar 

  56. Latini R, Masson S, Staszewsky L, Barlera S. Neurohormonal modulation in heart failure of ischemic etiology: correlates with left ventricular remodeling. Curr Heart Fail Rep. 2006;3(4):157–63. PubMed PMID: 17129508. Epub 2006/11/30. eng.

    CAS  PubMed  Google Scholar 

  57. Sardu C, Marfella R, Santulli G, Paolisso G. Functional role of miRNA in cardiac resynchronization therapy. Pharmacogenomics. 2014;15(8):1159–68. PubMed PMID: 25084208.

    CAS  PubMed  Google Scholar 

  58. Senni M, Paulus WJ, Gavazzi A, Fraser AG, Diez J, Solomon SD, et al. New strategies for heart failure with preserved ejection fraction: the importance of targeted therapies for heart failure phenotypes. Eur Heart J. 2014;35:2797–815. PubMed PMID: 25104786.

    Google Scholar 

  59. Perez-Alvarez A, Hernandez-Vivanco A, Albillos A. Past, present and future of human chromaffin cells: role in physiology and therapeutics. Cell Mol Neurobiol. 2010;30(8):1407–15. PubMed PMID: 21107679. Epub 2010/11/26. eng.

    CAS  PubMed  Google Scholar 

  60. Deo SH, Jenkins NT, Padilla J, Parrish AR, Fadel PJ. Norepinephrine increases NADPH oxidase-derived superoxide in human peripheral blood mononuclear cells via alpha-adrenergic receptors. Am J Physiol Regul Integr Comp Physiol. 2013;305(10):R1124–32. PubMed PMID: 24068047. Pubmed Central PMCID: 3841802.

    PubMed Central  CAS  PubMed  Google Scholar 

  61. Ma Y, Krueger JJ, Redmon SN, Uppuganti S, Nyman JS, Hahn MK, et al. Extracellular norepinephrine clearance by the norepinephrine transporter is required for skeletal homeostasis. J Biol Chem. 2013;288(42):30105–13. PubMed PMID: 24005671. Pubmed Central PMCID: 3798479.

    PubMed Central  CAS  PubMed  Google Scholar 

  62. Thireau J, Karam S, Roberge S, Roussel J, Aimond F, Cassan C, et al. Beta-adrenergic blockade combined with subcutaneous B-type natriuretic peptide: a promising approach to reduce ventricular arrhythmia in heart failure? Heart. 2014;100(11):833–41. PubMed PMID: 24667281.

    CAS  PubMed  Google Scholar 

  63. Staroukine M, Devriendt J, Decoodt P, Verniory A. Relationships between plasma epinephrine, norepinephrine, dopamine and angiotensin II concentrations, renin activity, hemodynamic state and prognosis in acute heart failure. Acta Cardiol. 1984;39(2):131–8. PubMed PMID: 6375223.

    CAS  PubMed  Google Scholar 

  64. Yuan Q, Chen Z, Santulli G, Gu L, Yang ZG, Yuan ZQ, et al. Functional Role of Calstabin2 in Age-related Cardiac Alterations. Scientific reports. 2014;4:7425. PubMed PMID: 25502776.

    Google Scholar 

  65. Moussouttas M, Mearns E, Walters A, DeCaro M. Plasma catecholamine profile of subarachnoid hemorrhage patients with neurogenic cardiomyopathy: a prospective study. J Cardiovasc Dis. 2014;2(3):125–30.

    CAS  Google Scholar 

  66. Santulli G. Importance of HDL increase in long-term cardiovascular effects of low-carbohydrate diet. Ann Intern Med. 2015; In press.

    Google Scholar 

  67. Huang CJ, Webb HE, Zourdos MC, Acevedo EO. Cardiovascular reactivity, stress, and physical activity. Front Physiol. 2013;4:314. PubMed PMID: 24223557. Pubmed Central PMCID: 3819592.

    PubMed Central  PubMed  Google Scholar 

  68. Weng TP, Fu TC, Wang CH, Hsu CC, Wang JS. Activation of lymphocyte autophagy/apoptosis reflects haemodynamic inefficiency and functional aerobic impairment in patients with heart failure. Clin Sci. 2014;127(10):589–602. PubMed PMID: 24863428.

    CAS  PubMed  Google Scholar 

  69. Berezin A, Kremzer A, Samura T, Martovitskaya Y. Apoptotic microparticles to progenitor mononuclear cells ratio in heart failure: relevance of clinical status and outcomes. J Cardiovasc Dis. 2014;2(2):50–7.

    Google Scholar 

  70. Ciccarelli M, Santulli G, Campanile A, Galasso G, Cervero P, Altobelli GG, et al. Endothelial alpha1-adrenoceptors regulate neo-angiogenesis. Br J Pharmacol. 2008;153(5):936–46. PubMed PMID: 18084315. Epub 2007/12/18. eng.

    PubMed Central  CAS  PubMed  Google Scholar 

  71. Gao W, Li J. Femoral artery occlusion increases muscle pressor reflex and expression of hypoxia-inducible factor-1α in sensory neurons. J Cardiovasc Dis. 2014;1(2):34–40.

    Google Scholar 

  72. Brinks H, Koch WJ. betaARKct: a therapeutic approach for improved adrenergic signaling and function in heart disease. J Cardiovasc Transl Res. 2010;3(5):499–506. PubMed PMID: 20623214.

    PubMed  Google Scholar 

  73. Gurdal H, Friedman E, Johnson MD. Beta-adrenoceptor-G alpha S coupling decreases with age in rat aorta. Mol Pharmacol. 1995;47(4):772–8. PubMed PMID: 7723738. Epub 1995/04/01. eng.

    CAS  PubMed  Google Scholar 

  74. Seals DR, Dinenno FA. Collateral damage: cardiovascular consequences of chronic sympathetic activation with human aging. Am J Physiol Heart Circ Physiol. 2004;287(5):H1895–905. PubMed PMID: 15475526.

    CAS  PubMed  Google Scholar 

  75. Santulli G, Campanile A, Spinelli L, di Panzillo Assante E, Ciccarelli M, Trimarco B, et al. G protein-coupled receptor kinase 2 in patients with acute myocardial infarction. Am J Cardiol. 2011;107(8):1125–30. PubMed PMID: 21296320. Epub 2011/02/08. eng.

    CAS  PubMed  Google Scholar 

  76. Buroker N. ADRBK1 (GRK2) rSNPs, transcriptional factor binding sites and cardiovascular disease in the black population. J Cardiovasc Dis. 2014;2(2):62–7.

    Google Scholar 

  77. Borkowski KR, Gros R, Schneider H. Vascular beta-adrenoceptor-mediated responses in hypertension and ageing in rats. J Auton Pharmacol. 1992;12(6):389–401. PubMed PMID: 1335455. Epub 1992/12/01. eng.

    CAS  PubMed  Google Scholar 

  78. Zhao L, Yang F, Xu K, Cao H, Zheng GY, Zhang Y, et al. Common genetic variants of the beta2-adrenergic receptor affect its translational efficiency and are associated with human longevity. Aging Cell. 2012;11(6):1094–101. PubMed PMID: 23020224. Pubmed Central PMCID: 3633790.

    PubMed Central  CAS  PubMed  Google Scholar 

  79. Renard P, Kovalski JL, Cochereau I, Jaulerry S, Williamson W, Elena PP, et al. Comparison of carteolol plasmatic levels after repeated instillations of long-acting and regular formulations of carteolol 2% in glaucoma patients. Graefes Arch Clin Exp Ophthalmol Albrecht von Graefes Arch Klin Exp Ophthalmol. 2005;243(12):1221–7. PubMed PMID: 16003515. Epub 2005/07/09. eng.

    CAS  Google Scholar 

  80. Tang-Liu DD, Shackleton M, Richman JB. Ocular metabolism of levobunolol. J Ocul Pharmacol. 1988;4(3):269–78. PubMed PMID: 3058836. Epub 1988/01/01. eng.

    CAS  PubMed  Google Scholar 

  81. Heel RC, Brogden RN, Pakes GE, Speight TM, Avery GS. Nadolol: a review of its pharmacological properties and therapeutic efficacy in hypertension and angina pectoris. Drugs. 1980;20(1):1–23. PubMed PMID: 6105067. Epub 1980/07/01. eng.

    CAS  PubMed  Google Scholar 

  82. Muller FO, Hundt HK, Bromley PA, Torres J, Vanderbeke O. Single and divided doses of penbutolol. Clin Pharmacol Ther. 1979;25(5 Pt 1):528–35. PubMed PMID: 436357. Epub 1979/05/01. eng.

    CAS  PubMed  Google Scholar 

  83. Golightly LK. Pindolol: a review of its pharmacology, pharmacokinetics, clinical uses, and adverse effects. Pharmacotherapy. 1982;2(3):134–47. PubMed PMID: 6133267. Epub 1982/05/01. eng.

    CAS  PubMed  Google Scholar 

  84. Mackichan JJ, Pyszczynski DR, Jusko WJ. Dose-dependent disposition of oral propranolol in normal subjects. Biopharm Drug Dispos. 1980;1(4):159–66. PubMed PMID: 7448344. Epub 1980/04/01. eng.

    CAS  PubMed  Google Scholar 

  85. Schnelle K, Klein G, Schinz A. Studies on the pharmacokinetics and pharmacodynamics of the beta-adrenergic blocking agent sotalol in normal man. J Clin Pharmacol. 1979;19(8–9 Pt 2):516–22. PubMed PMID: 489770. Epub 1979/08/01. eng.

    CAS  PubMed  Google Scholar 

  86. Else OF, Sorenson H, Edwards IR. Plasma timolol levels after oral and intravenous administration. Eur J Clin Pharmacol. 1978;14(6):431–4. PubMed PMID: 738350. Epub 1978/12/18. eng.

    CAS  PubMed  Google Scholar 

  87. Singh BN, Thoden WR, Wahl J. Acebutolol: a review of its pharmacology, pharmacokinetics, clinical uses, and adverse effects. Pharmacotherapy. 1986;6(2):45–63. PubMed PMID: 3012486. Epub 1986/03/01. eng.

    CAS  PubMed  Google Scholar 

  88. Wan SH, Koda RT, Maronde RF. Pharmacokinetics, pharmacology of atenolol and effect of renal disease. Br J Clin Pharmacol. 1979;7(6):569–74. PubMed PMID: 465278. Pubmed Central PMCID: 1429677. Epub 1979/06/01. eng.

    PubMed Central  CAS  PubMed  Google Scholar 

  89. Frishman WH, Tepper D, Lazar EJ, Behrman D. Betaxolol: a new long-acting beta 1-selective adrenergic blocker. J Clin Pharmacol. 1990;30(8):686–92. PubMed PMID: 2205635. Epub 1990/08/01. eng.

    CAS  PubMed  Google Scholar 

  90. Le Coz F, Sauleman P, Poirier JM, Cuche JL, Midavaine M, Rames A, et al. Oral pharmacokinetics of bisoprolol in resting and exercising healthy volunteers. J Cardiovasc Pharmacol. 1991;18(1):28–34. PubMed PMID: 1719288. Epub 1991/07/01. eng.

    PubMed  Google Scholar 

  91. Garnock-Jones KP. Esmolol: a review of its use in the short-term treatment of tachyarrhythmias and the short-term control of tachycardia and hypertension. Drugs. 2012;72(1):109–32. PubMed PMID: 22191799. Epub 2011/12/24. eng.

    CAS  PubMed  Google Scholar 

  92. Kukin ML, Mannino MM, Freudenberger RS, Kalman J, Buchholz-Varley C, Ocampo O. Hemodynamic comparison of twice daily metoprolol tartrate with once daily metoprolol succinate in congestive heart failure. J Am Coll Cardiol. 2000;35(1):45–50. PubMed PMID: 10636257. Epub 2000/01/15. eng.

    CAS  PubMed  Google Scholar 

  93. Andreka P, Aiyar N, Olson LC, Wei JQ, Turner MS, Webster KA, et al. Bucindolol displays intrinsic sympathomimetic activity in human myocardium. Circulation. 2002;105(20):2429–34. PubMed PMID: 12021232. Epub 2002/05/22. eng.

    CAS  PubMed  Google Scholar 

  94. Sehrt D, Meineke I, Tzvetkov M, Gultepe S, Brockmoller J. Carvedilol pharmacokinetics and pharmacodynamics in relation to CYP2D6 and ADRB pharmacogenetics. Pharmacogenomics. 2011;12(6):783–95. PubMed PMID: 21599570. Epub 2011/05/24. eng.

    CAS  PubMed  Google Scholar 

  95. Riddell JG, Shanks RG, Brogden RN. Celiprolol. A preliminary review of its pharmacodynamic and pharmacokinetic properties and its therapeutic use in hypertension and angina pectoris. Drugs. 1987;34(4):438–58. PubMed PMID: 2890513. Epub 1987/10/01. eng.

    CAS  PubMed  Google Scholar 

  96. Lalonde RL, O’Rear TL, Wainer IW, Drda KD, Herring VL, Bottorff MB. Labetalol pharmacokinetics and pharmacodynamics: evidence of stereoselective disposition. Clin Pharmacol Ther. 1990;48(5):509–19. PubMed PMID: 2225711. Epub 1990/11/01. eng.

    CAS  PubMed  Google Scholar 

  97. de Nigris F, Mancini FP, Balestrieri ML, Byrns R, Fiorito C, Williams-Ignarro S, et al. Therapeutic dose of nebivolol, a nitric oxide-releasing beta-blocker, reduces atherosclerosis in cholesterol-fed rabbits. Nitric Oxide Biol Chem Off J Nitric Oxide Soc. 2008;19(1):57–63. PubMed PMID: 18435936. Epub 2008/04/26. eng.

    Google Scholar 

  98. Llewellyn TL, Sharma NM, Zheng H, Patel KP. Effects of exercise training on SFO-mediated sympathoexcitation during chronic heart failure. Am J Physiol Heart Circ Physiol. 2014;306(1):H121–31. PubMed PMID: 24163080. Pubmed Central PMCID: 3920154. Epub 2013/10/29. eng.

    PubMed Central  CAS  PubMed  Google Scholar 

  99. Kukin ML. Beta-blockers in chronic heart failure: considerations for selecting an agent. Mayo Clin Proc. 2002;77(11):1199–206. PubMed PMID: 12440556. Epub 2002/11/21. eng.

    CAS  PubMed  Google Scholar 

  100. Ellison KE, Gandhi G. Optimising the use of beta-adrenoceptor antagonists in coronary artery disease. Drugs. 2005;65(6):787–97. PubMed PMID: 15819591. Epub 2005/04/12. eng.

    CAS  PubMed  Google Scholar 

  101. Rochais F, Vilardaga JP, Nikolaev VO, Bunemann M, Lohse MJ, Engelhardt S. Real-time optical recording of beta1-adrenergic receptor activation reveals supersensitivity of the Arg389 variant to carvedilol. J Clin Invest. 2007;117(1):229–35. PubMed PMID: 17200720. Pubmed Central PMCID: 1751291. Epub 2007/01/04. eng.

    PubMed Central  CAS  PubMed  Google Scholar 

  102. DeGeorge Jr BR, Koch WJ. Beta blocker specificity: a building block toward personalized medicine. J Clin Invest. 2007;117(1):86–9. PubMed PMID: 17200711. Pubmed Central PMCID: 1716219. Epub 2007/01/04. eng.

    PubMed Central  CAS  PubMed  Google Scholar 

  103. Podowski M, Calvi C, Metzger S, Misono K, Poonyagariyagorn H, Lopez-Mercado A, et al. Angiotensin receptor blockade attenuates cigarette smoke-induced lung injury and rescues lung architecture in mice. J Clin Invest. 2012;122(1):229–40. PubMed PMID: 22182843. Pubmed Central PMCID: 3248282. Epub 2011/12/21. eng.

    PubMed Central  CAS  PubMed  Google Scholar 

  104. Santulli G. Beta-Blockers in diabetic patients with heart failure. JAMA Intern Med. 2015; In press.

    Google Scholar 

  105. Lazalde-Ramos BP, Martinez-Fierro Mde L, Galaviz-Hernandez C, Garza-Veloz I, Naranjo ME, Sosa-Macias M, et al. CYP2D6 gene polymorphisms and predicted phenotypes in eight indigenous groups from northwestern Mexico. Pharmacogenomics. 2014;15(3):339–48. PubMed PMID: 24533713. Epub 2014/02/19. eng.

    CAS  PubMed  Google Scholar 

  106. Sim SC, Kacevska M, Ingelman-Sundberg M. Pharmacogenomics of drug-metabolizing enzymes: a recent update on clinical implications and endogenous effects. Pharmacogenomics J. 2013;13(1):1–11. PubMed PMID: 23089672. Epub 2012/10/24. eng.

    CAS  PubMed  Google Scholar 

  107. Tendera M, Ochala A. Overview of the results of recent beta blocker trials. Curr Opin Cardiol. 2001;16(3):180–5. PubMed PMID: 11357013. Epub 2001/05/18. eng.

    CAS  PubMed  Google Scholar 

  108. Kurdi M, Booz GW. Carvedilol protects the infarcted heart by upregulating miR-133: first evidence that disease state affects beta-adrenergic arrestin-biased signaling? J Mol Cell Cardiol. 2014;76:12–4. PubMed PMID: 25128784. Epub 2014/08/17. Eng.

    CAS  PubMed  Google Scholar 

  109. Vaidya V, Patel P. Health expenditure comparison of extended-release metoprolol succinate and immediate-release metoprolol tartrate. Clinico Econ Outcomes Res CEOR. 2012;4:49–56. PubMed PMID: 22359463. Pubmed Central PMCID: 3284258. Epub 2012/02/24. eng.

    Google Scholar 

  110. Zhao N, Zidan A, Tawakkul M, Sayeed VA, Khan M. Tablet splitting: product quality assessment of metoprolol succinate extended release tablets. Int J Pharm. 2010;401(1–2):25–31. PubMed PMID: 20849940. Epub 2010/09/21. eng.

    CAS  PubMed  Google Scholar 

  111. Cheng JW. A review of isosorbide dinitrate and hydralazine in the management of heart failure in black patients, with a focus on a new fixed-dose combination. Clin Ther. 2006;28(5):666–78. PubMed PMID: 16861089. Epub 2006/07/25. eng.

    CAS  PubMed  Google Scholar 

  112. Oparil S, Davis BR, Cushman WC, Ford CE, Furberg CD, Habib GB, et al. Mortality and morbidity during and after antihypertensive and lipid-lowering treatment to prevent heart attack trial: results by sex. Hypertension. 2013;61(5):977–86. PubMed PMID: 23529173. Pubmed Central PMCID: 4114223. Epub 2013/03/27. eng.

    PubMed Central  CAS  PubMed  Google Scholar 

  113. Gavras I, Manolis AJ, Gavras H. The alpha2 -adrenergic receptors in hypertension and heart failure: experimental and clinical studies. J Hypertens. 2001;19(12):2115–24. PubMed PMID: 11725152. Epub 2001/11/29. eng.

    CAS  PubMed  Google Scholar 

  114. Pocock S, Wilhelmsen L, Dickstein K, Francis G, Wittes J. The data monitoring experience in the MOXCON trial. Eur Heart J. 2004;25(22):1974–8. PubMed PMID: 15541832.

    PubMed  Google Scholar 

  115. Frantz RP, Lowes BD, Grayburn PA, White M, Krause-Steinrauf H, Krishnan V, et al. Baseline and serial neurohormones in patients with congestive heart failure treated with and without bucindolol: results of the neurohumoral substudy of the Beta-Blocker Evaluation of Survival Study (BEST). J Card Fail. 2007;13(6):437–44. PubMed PMID: 17675057.

    CAS  PubMed  Google Scholar 

  116. Deneer VH, van Hemel NM. Is antiarrhythmic treatment in the elderly different? a review of the specific changes. Drugs Aging. 2011;28(8):617–33. PubMed PMID: 21812498. Epub 2011/08/05. eng.

    CAS  PubMed  Google Scholar 

  117. Chaney E, Shaw A. Pathophysiology of fluid retention in heart failure. Contrib Nephrol. 2010;164:46–53. PubMed PMID: 20427993. Epub 2010/04/30. eng.

    PubMed  Google Scholar 

  118. Struthers AD, MacDonald TM. Review of aldosterone- and angiotensin II-induced target organ damage and prevention. Cardiovasc Res. 2004;61(4):663–70. PubMed PMID: 14985063. Epub 2004/02/27. eng.

    CAS  PubMed  Google Scholar 

  119. Chrissobolis S, Drummond GR, Faraci FM, Sobey CG. Chronic aldosterone administration causes Nox2-mediated increases in reactive oxygen species production and endothelial dysfunction in the cerebral circulation. J Hypertens. 2014;32(9):1815–21. PubMed PMID: 24991871. Epub 2014/07/06. eng.

    PubMed Central  CAS  PubMed  Google Scholar 

  120. Galmiche G, Pizard A, Gueret A, El Moghrabi S, Ouvrard-Pascaud A, Berger S, et al. Smooth muscle cell mineralocorticoid receptors are mandatory for aldosterone-salt to induce vascular stiffness. Hypertension. 2014;63(3):520–6. PubMed PMID: 24296280. Epub 2013/12/04. eng.

    CAS  PubMed  Google Scholar 

  121. Gradman AH, Papademetriou V. Combined renin-angiotensin-aldosterone system inhibition in patients with chronic heart failure secondary to left ventricular systolic dysfunction. Am Heart J. 2009;157(6 Suppl):S17–23. PubMed PMID: 19450720.

    CAS  PubMed  Google Scholar 

  122. Regnault V, Lagrange J, Pizard A, Safar ME, Fay R, Pitt B, et al. Opposite predictive value of pulse pressure and aortic pulse wave velocity on heart failure with reduced left ventricular ejection fraction: insights from an Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS) substudy. Hypertension. 2014;63(1):105–11. PubMed PMID: 24126172.

    CAS  PubMed  Google Scholar 

  123. Wittes J, Palensky J, Asner D, Julian D, Boissel JP, Furberg CD, et al. Experience collecting interim data on mortality: an example from the RALES study. Curr Control Trials Cardiovasc Med. 2001;2(1):59–62. PubMed PMID: 11806773. Pubmed Central PMCID: 56203.

    PubMed Central  PubMed  Google Scholar 

  124. Wang HJ, Wang W, Cornish KG, Rozanski GJ, Zucker IH. Cardiac sympathetic afferent denervation attenuates cardiac remodeling and improves cardiovascular dysfunction in rats with heart failure. Hypertension. 2014;64:745–55. PubMed PMID: 24980663.

    CAS  PubMed  Google Scholar 

  125. Katayama T, Sueta D, Kataoka K, Hasegawa Y, Koibuchi N, Toyama K, et al. Long-term renal denervation normalizes disrupted blood pressure circadian rhythm and ameliorates cardiovascular injury in a rat model of metabolic syndrome. J Am Heart Assoc. 2013;2(4):e000197. PubMed PMID: 23974905. Pubmed Central PMCID: 3828797.

    PubMed Central  PubMed  Google Scholar 

  126. Molon G, Marczyk J, Virzi G, Bellazzi R, Malovini A, Accardi F, et al. Analysis of ECG by means of complexity index and association with clinical response to cardiac resynchronization therapy. J Cardiovasc Dis. 2014;2(3):147–52.

    Google Scholar 

  127. Cha YM, Chareonthaitawee P, Dong YX, Kemp BJ, Oh JK, Miyazaki C, et al. Cardiac sympathetic reserve and response to cardiac resynchronization therapy. Circ Heart Fail. 2011;4(3):339–44. PubMed PMID: 21421772.

    PubMed  Google Scholar 

  128. Santulli G, D’Ascia S, D’Ascia C. Regarding the impact of left ventricular size on response to cardiac resynchronization therapy. Am Heart J. 2012;163(4):e11. PubMed PMID: 22520543. Epub 2012/04/24. eng.

    PubMed  Google Scholar 

  129. Santulli G, D’Ascia C. Atrial remodelling in echocardiographic super-responders to cardiac resynchronization therapy. Heart. 2012;98(6):517. author reply PubMed PMID: 22350031. Epub 2012/02/22. eng.

    PubMed  Google Scholar 

  130. Szepietowska B, Zhu W, Czyzyk J, Eid T, Sherwin RS. EphA5-EphrinA5 interactions within the ventromedial hypothalamus influence counterregulatory hormone release and local glutamine/glutamate balance during hypoglycemia. Diabetes. 2013;62(4):1282–8. PubMed PMID: 23274893. Pubmed Central PMCID: 3609598.

    PubMed Central  CAS  PubMed  Google Scholar 

  131. Neglia D, De Caterina A, Marraccini P, Natali A, Ciardetti M, Vecoli C, et al. Impaired myocardial metabolic reserve and substrate selection flexibility during stress in patients with idiopathic dilated cardiomyopathy. Am J Physiol Heart Circ Physiol. 2007;293(6):H3270–8. PubMed PMID: 17921325.

    CAS  PubMed  Google Scholar 

  132. Dias P, Terracciano CM. Hyperpolarization-activated cyclic nucleotide-gated channels and ventricular arrhythmias in heart failure: a novel target for therapy? J Am Heart Assoc. 2013;2(3):e000287. PubMed PMID: 23747794. Pubmed Central PMCID: 3698796.

    PubMed Central  PubMed  Google Scholar 

  133. Li YF, Shi ST. Age-dependent differential crosstalk between alpha(1)-adrenergic and angiotensin receptors. Can J Cardiol. 2009;25(8):481–5. PubMed PMID: 19668783. Pubmed Central PMCID: 2732376.

    PubMed Central  PubMed  Google Scholar 

  134. Ciccarelli M, Santulli G, Pascale V, Trimarco B, Iaccarino G. Adrenergic receptors and metabolism: role in development of cardiovascular disease. Front Physiol. 2013;4:265. PubMed PMID: 24106479. Pubmed Central PMCID: 3789271.

    PubMed Central  PubMed  Google Scholar 

  135. Chakraborty M, Phillips A, Macdonald J, Windsor J, Hickey A. Mitochondrial respiration in mononuclear cells and heart fibers in spontaneously hypertensive rats. J Cardiovasc Dis. 2014;2(1):7–14.

    CAS  Google Scholar 

  136. Santulli G, Marks AR. Essential roles of intracellular calcium release channels in muscle, brain, metabolism, and aging. Current Molecular Pharmacology. 2015; In press.

    Google Scholar 

  137. Fu Q, Xu B, Liu Y, Parikh D, Li J, Li Y, et al. Insulin inhibits cardiac contractility by inducing a Gi-biased beta2 adrenergic signaling in hearts. Diabetes. 2014;63:2676–89. PubMed PMID: 24677713.

    CAS  PubMed  Google Scholar 

  138. Msolly A, Miled A, Kassab A. Hydrogen peroxide: an oxidant stress indicator in Type 2 diabetes mellitus. J Cardiovasc Dis. 2014;1(2):48–52.

    Google Scholar 

  139. Oriente F, Iovino S, Cassese A, Romano C, Miele C, Troncone G, et al. Overproduction of phosphoprotein enriched in diabetes (PED) induces mesangial expansion and upregulates protein kinase C-beta activity and TGF-beta1 expression. Diabetologia. 2009;52(12):2642–52. PubMed PMID: 19789852. Epub 2009/10/01. eng.

    CAS  PubMed  Google Scholar 

  140. Azevedo PS, Minicucci MF, Santos PP, Paiva SA, Zornoff LA. Energy metabolism in cardiac remodeling and heart failure. Cardiol Rev. 2013;21(3):135–40. PubMed PMID: 22990373.

    PubMed  Google Scholar 

  141. Shimizu I, Minamino T, Toko H, Okada S, Ikeda H, Yasuda N, et al. Excessive cardiac insulin signaling exacerbates systolic dysfunction induced by pressure overload in rodents. J Clin Invest. 2010;120(5):1506–14. PubMed PMID: 20407209. Pubmed Central PMCID: 2860916.

    PubMed Central  CAS  PubMed  Google Scholar 

  142. Badimon L, Hernandez Vera R, Vilahur G. Determinants of cardiovascular risk in diabetes beyond hyperglycemia. J Cardiovasc Dis. 2014;1(2):53–62.

    Google Scholar 

  143. Masuo K, Rakugi H, Ogihara T, Lambert GW. Different mechanisms in weight loss-induced blood pressure reduction between a calorie-restricted diet and exercise. Hypertens Res Off J Japan Soc Hypertens. 2012;35(1):41–7. PubMed PMID: 21814218. Epub 2011/08/05. eng.

    CAS  Google Scholar 

  144. Quinones MJ, Nicholas SB, Lyon CJ. Insulin resistance and the endothelium. Curr Diab Rep. 2005;5(4):246–53. PubMed PMID: 16033673.

    CAS  PubMed  Google Scholar 

  145. Mongillo M, John AS, Leccisotti L, Pennell DJ, Camici PG. Myocardial pre-synaptic sympathetic function correlates with glucose uptake in the failing human heart. Eur J Nucl Med Mol Imaging. 2007;34(8):1172–7. PubMed PMID: 17294189.

    PubMed  Google Scholar 

  146. Larsen TM, Toubro S, van Baak MA, Gottesdiener KM, Larson P, Saris WH, et al. Effect of a 28-d treatment with L-796568, a novel beta(3)-adrenergic receptor agonist, on energy expenditure and body composition in obese men. Am J Clin Nutr. 2002;76(4):780–8. PubMed PMID: 12324291.

    CAS  PubMed  Google Scholar 

  147. Fusco A, Santulli G, Sorriento D, Cipolletta E, Garbi C, Dorn 2nd GW, et al. Mitochondrial localization unveils a novel role for GRK2 in organelle biogenesis. Cell Signal. 2012;24(2):468–75. PubMed PMID: 21983013. Pubmed Central PMCID: 3237777.

    PubMed Central  CAS  PubMed  Google Scholar 

  148. Chen M, Sato PY, Chuprun JK, Peroutka RJ, Otis NJ, Ibetti J, et al. Prodeath signaling of G protein-coupled receptor kinase 2 in cardiac myocytes after ischemic stress occurs via extracellular signal-regulated kinase-dependent heat shock protein 90-mediated mitochondrial targeting. Circ Res. 2013;112(8):1121–34. PubMed PMID: 23467820. Pubmed Central PMCID: 3908784.

    PubMed Central  CAS  PubMed  Google Scholar 

  149. Taguchi K, Sakata K, Ohashi W, Imaizumi T, Imura J, Hattori Y. Tonic inhibition by G protein-coupled receptor kinase 2 of Akt/endothelial nitric-oxide synthase signaling in human vascular endothelial cells under conditions of hyperglycemia with high insulin levels. J Pharmacol Exp Ther. 2014;349(2):199–208. PubMed PMID: 24570070.

    PubMed  Google Scholar 

  150. Hata JA, Williams ML, Koch WJ. Genetic manipulation of myocardial beta-adrenergic receptor activation and desensitization. J Mol Cell Cardiol. 2004;37(1):11–21. PubMed PMID: 15242731.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Gaetano Santulli MD, PhD .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Santulli, G. (2015). Sympathetic Nervous System Signaling in Heart Failure and Cardiac Aging. In: Jagadeesh, G., Balakumar, P., Maung-U, K. (eds) Pathophysiology and Pharmacotherapy of Cardiovascular Disease. Adis, Cham. https://doi.org/10.1007/978-3-319-15961-4_5

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-15961-4_5

  • Publisher Name: Adis, Cham

  • Print ISBN: 978-3-319-15960-7

  • Online ISBN: 978-3-319-15961-4

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics