title: Central neural control of sympathetic nerve activity in heart failure following exercise training.
abstract: Typical characteristics of chronic congestive heart failure (HF) are increased sympathetic drive, altered autonomic reflexes, and altered body fluid regulation. These abnormalities lead to an increased risk of mortality, particularly in the late stage of chronic HF. Recent evidence suggests that central nervous system (CNS) mechanisms may be important in these abnormalities during HF. Exercise training (ExT) has emerged as a nonpharmacological therapeutic strategy substitute with significant benefit to patients with HF. Regular ExT improves functional capacity as well as quality of life and perhaps prognosis in chronic HF patients. The mechanism(s) by which ExT improves the clinical status of HF patients is not fully known. Recent studies have provided convincing evidence that ExT significantly alleviates the increased sympathetic drive, altered autonomic reflexes, and altered body fluid regulation in HF. This review describes and highlights the studies that examine various central pathways involved in autonomic outflow that are altered in HF and are improved following ExT. The increased sympathoexcitation is due to an imbalance between inhibitory and excitatory mechanisms within specific areas in the CNS such as the paraventricular nucleus (PVN) of the hypothalamus. Studies summarized here have revealed that ExT improves the altered inhibitory pathway utilizing nitric oxide and GABA mechanisms within the PVN in HF. ExT alleviates elevated sympathetic outflow in HF through normalization of excitatory glutamatergic and angiotensinergic mechanisms within the PVN. ExT also improves volume reflex function and thus fluid balance in HF. Preliminary observations also suggest that ExT induces structural neuroplasticity in the brain of rats with HF. We conclude that improvement of the enhanced CNS-mediated increase in sympathetic outflow, specifically to the kidneys related to fluid balance, contributes to the beneficial effects of ExT in HF.
authors.affiliation: Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, NE 68198-5850, USA. kpatel@unmc.edu
authors.forename: Kaushik P
authors.initials: KP
authors.lastname: Patel
authors.forename: Hong
authors.initials: H
authors.lastname: Zheng
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005081:Exercise Therapy; D006321:Heart / Q000294:innervation / Q000502:physiology*; D006333:Heart Failure / Q000503:physiopathology* / Q000628:therapy*; D006801:Humans; D010286:Paraventricular Hypothalamic Nucleus / Q000502:physiology; D013564:Sympathetic Nervous System / Q000502:physiology*
references.citation: Annu Rev Neurosci. 1994;17:153-83
references.pmid: 7516125
references.citation: Am J Physiol Heart Circ Physiol. 2002 Jul;283(1):H423-33
references.pmid: 12063317
references.citation: J Appl Physiol (1985). 2002 Jun;92(6):2403-8
references.pmid: 12015354
references.citation: Clin Exp Pharmacol Physiol. 1998 Jun;25(6):474-8
references.pmid: 9673828
references.citation: Clin Exp Pharmacol Physiol. 2001 Jan-Feb;28(1-2):95-9
references.pmid: 11153547
references.citation: Acta Physiol Scand. 1994 Mar;150(3):259-66
references.pmid: 8010133
references.citation: Am J Physiol. 1995 Nov;269(5 Pt 2):R1189-96
references.pmid: 7503310
references.citation: Pharmacol Ther. 2004 Aug;103(2):109-20
references.pmid: 15369679
references.citation: J Am Coll Cardiol. 1997 Mar 1;29(3):597-603
references.pmid: 9060899
references.citation: Curr Opin Psychiatry. 2010 Nov;23(6):491-7
references.pmid: 20733494
references.citation: Acta Physiol Scand. 2001 Mar;171(3):295-303
references.pmid: 11412141
references.citation: Circulation. 1988 Apr;77(4):721-30
references.pmid: 3280156
references.citation: Am J Physiol Regul Integr Comp Physiol. 2002 Apr;282(4):R1006-15
references.pmid: 11893604
references.citation: Brain Res. 1983 Apr 11;265(1):55-61
references.pmid: 6850321
references.citation: Am J Physiol. 1992 Jun;262(6 Pt 2):H1640-5
references.pmid: 1621825
references.citation: Exp Physiol. 2008 May;93(5):694-700
references.pmid: 18356558
references.citation: EXS. 1996;76:1-19
references.pmid: 8805785
references.citation: Brain Res. 1982 Mar 11;235(2):315-25
references.pmid: 7188330
references.citation: Auton Neurosci. 2005 Aug 31;121(1-2):56-63
references.pmid: 16099221
references.citation: Curr Cardiol Rep. 2008 May;10(3):190-7
references.pmid: 18489862
references.citation: Kidney Int. 1973 Nov;4(5):309-17
references.pmid: 4762578
references.citation: Hypertension. 2007 Apr;49(4):926-31
references.pmid: 17325232
references.citation: Hypertension. 2007 Oct;50(4):780-5
references.pmid: 17646572
references.citation: Circ Res. 2003 Nov 14;93(10):990-7
references.pmid: 14576197
references.citation: Baillieres Clin Neurol. 1997 Jul;6(2):283-96
references.pmid: 9483294
references.citation: Circulation. 1996 Jan 15;93(2):210-4
references.pmid: 8548890
references.citation: Front Aging Neurosci. 2010 Aug 26;2:
references.pmid: 20890449
references.citation: Am J Physiol Regul Integr Comp Physiol. 2008 Jun;294(6):R1863-72
references.pmid: 18385465
references.citation: Circulation. 2003 Mar 4;107(8):1210-25
references.pmid: 12615804
references.citation: Am J Physiol Renal Physiol. 2006 Dec;291(6):F1148-56
references.pmid: 16822936
references.citation: Basic Res Cardiol. 1996;91 Suppl 1:31-6
references.pmid: 8896741
references.citation: J Physiol. 1998 May 1;508 ( Pt 3):929-35
references.pmid: 9518743
references.citation: Heart. 1997 Nov;78(5):431-6
references.pmid: 9414999
references.citation: Regul Pept. 1996 Nov 14;67(1):21-5
references.pmid: 8952001
references.citation: Am J Physiol Heart Circ Physiol. 2003 Oct;285(4):H1738-46
references.pmid: 12969886
references.citation: Brain Res. 1998 Mar 9;786(1-2):219-25
references.pmid: 9555024
references.citation: Am J Cardiol. 1978 Sep;42(3):372-6
references.pmid: 685849
references.citation: Circulation. 2007 Jun 19;115(24):3095-102
references.pmid: 17548725
references.citation: J Appl Physiol (1985). 2010 Apr;108(4):923-32
references.pmid: 20093667
references.citation: Annu Rev Neurosci. 2005;28:377-401
references.pmid: 16022601
references.citation: Am J Physiol. 1996 Oct;271(4 Pt 2):H1441-8
references.pmid: 8897938
references.citation: Intern Med. 1998 Feb;37(2):112-22
references.pmid: 9550589
references.citation: J Appl Physiol (1985). 2005 Feb;98(2):572-8
references.pmid: 15475607
references.citation: Prog Cardiovasc Dis. 1995 May-Jun;37(6):397-414
references.pmid: 7777669
references.citation: J Appl Physiol (1985). 2008 Sep;105(3):782-90
references.pmid: 18583379
references.citation: J Card Fail. 1999 Sep;5(3):188-94
references.pmid: 10496191
references.citation: J Am Coll Cardiol. 2003 Sep 3;42(5):854-60
references.pmid: 12957432
references.citation: Am J Physiol. 1995 Jan;268(1 Pt 2):H218-25
references.pmid: 7840266
references.citation: Am J Physiol. 1998 Dec;275(6):H2140-6
references.pmid: 9843814
references.citation: Am J Physiol. 1993 Oct;265(4 Pt 2):R923-8
references.pmid: 8238466
references.citation: Eur J Heart Fail. 2007 Jun-Jul;9(6-7):630-6
references.pmid: 17475552
references.citation: Circulation. 2000 Oct 10;102(15):1854-62
references.pmid: 11023943
references.citation: Am J Physiol Heart Circ Physiol. 2004 Nov;287(5):H2138-46
references.pmid: 15475532
references.citation: Am J Physiol Heart Circ Physiol. 2005 May;288(5):H2332-41
references.pmid: 15653768
references.citation: J Hypertens Suppl. 1989 Dec;7(6):S236-7
references.pmid: 2534408
references.citation: J Neurosci. 2001 Mar 1;21(5):1628-34
references.pmid: 11222653
references.citation: Cardiovasc Res. 2008 Sep 1;79(4):671-8
references.pmid: 18469338
references.citation: Brain Res. 1984 May 28;301(1):111-9
references.pmid: 6329435
references.citation: Brain Res. 2000 May 19;865(1):27-34
references.pmid: 10814730
references.citation: Am J Physiol Heart Circ Physiol. 2001 Sep;281(3):H995-1004
references.pmid: 11514264
references.citation: Circ Res. 2004 Oct 29;95(9):937-44
references.pmid: 15459075
references.citation: JAMA. 2009 Apr 8;301(14):1439-50
references.pmid: 19351941
references.citation: Am J Physiol. 1997 Sep;273(3 Pt 2):R864-72
references.pmid: 9321861
references.citation: Am J Physiol Regul Integr Comp Physiol. 2006 Feb;290(2):R383-92
references.pmid: 16179489
references.citation: J Appl Physiol (1985). 2005 Dec;99(6):2312-22
references.pmid: 16123206
references.citation: Circ Res. 1996 Jan;78(1):58-64
references.pmid: 8603506
references.citation: Exp Physiol. 2005 Mar;90(2):169-73
references.pmid: 15604110
references.citation: Brain Res Mol Brain Res. 2001 Nov 1;95(1-2):48-54
references.pmid: 11687276
references.citation: BMC Neurosci. 2009 Dec 04;10:144
references.pmid: 19961582
references.citation: Am J Physiol Regul Integr Comp Physiol. 2009 Nov;297(5):R1364-74
references.pmid: 19710393
references.citation: Circ Res. 2008 Mar 28;102(6):729-36
references.pmid: 18258853
references.citation: Brain Res. 1988 Jun 28;454(1-2):123-30
references.pmid: 2900661
references.citation: J Neurophysiol. 2002 Oct;88(4):1655-63
references.pmid: 12364495
references.citation: Am J Physiol Regul Integr Comp Physiol. 2000 Mar;278(3):R556-62
references.pmid: 10712272
references.citation: Hypertension. 1994 Oct;24(4):451-6
references.pmid: 8088910
references.citation: Clin Exp Pharmacol Physiol. 2007 Apr;34(4):377-84
references.pmid: 17324153
references.citation: J Physiol. 1996 Nov 1;496 ( Pt 3):749-57
references.pmid: 8930841
references.citation: Proc Soc Exp Biol Med. 1993 Apr;202(4):401-6
references.pmid: 8456103
references.citation: J Appl Physiol (1985). 2007 Feb;102(2):803-13
references.pmid: 17053106
references.citation: J Comp Neurol. 2000 Jul 3;422(3):352-62
references.pmid: 10861512
references.citation: Brain Res. 2009 Jun 1;1273:9-17
references.pmid: 19358834
references.citation: Am J Physiol. 1988 Jun;254(6 Pt 2):R1017-24
references.pmid: 3381907
references.citation: J Hypertens. 1985 Apr;3(2):117-29
references.pmid: 2991369