title: Muscle mechanoreflex overactivity in hypertension: a role for centrally-derived nitric oxide.
abstract: The cardiovascular response to exercise is abnormally large in hypertension. Over the past decade, it has become clear that the exercise pressor reflex (a peripheral feed-back mechanism originating in skeletal muscle) contributes significantly to the generation of this hyper-responsiveness. Further, it has been determined that overactivity of the mechanically (muscle mechanoreflex) and chemically (muscle metaboreflex) sensitive components of the exercise pressor reflex underpin its dysfunction. Given the recent attention in the literature, this review focuses upon the aberrant function of the muscle mechanoreflex in this disease. Evidence supporting a role for the mechanoreflex in the pathogenesis of the exaggerated cardiovascular response to physical activity is highlighted. The peripheral and central mechanisms that may be responsible for mechanoreflex overactivity in hypertension are likewise discussed. Particular attention is given to emerging evidence implicating a role for centrally-derived nitric oxide in this process.
authors: Department of Health Care Sciences, University of Texas Southwestern Medical Center, Dallas, TX, United States; Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, United States. Electronic address: scott.smith@utsouthwestern.edu.
authors: Scott A
authors: SA
authors: Smith
authors: Department of Kinesiology, Berry College, Mount Berry, GA, United States.
authors: Anna K
authors: AK
authors: Leal
authors: Department of Applied Physiology and Wellness, Southern Methodist University, Dallas, TX, United States.
authors: Megan N
authors: MN
authors: Murphy
authors: Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, United States.
authors: Ryan M
authors: RM
authors: Downey
authors: Department of Health Care Sciences, University of Texas Southwestern Medical Center, Dallas, TX, United States; Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, United States.
authors: Masaki
authors: M
authors: Mizuno
mesh_terms: D000818:Animals; D015444:Exercise / Q000502:physiology*; D006801:Humans; D006973:Hypertension / Q000473:pathology*; D009119:Muscle Contraction / Q000502:physiology*; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009569:Nitric Oxide / Q000378:metabolism*
chemical_list: D009569:Nitric Oxide
keywords: Autonomic nervous system; Blood pressure; Exercise; Heart rate; Hemodynamics; Sympathetic activity
references: J Physiol. 2011 Dec 15;589(Pt 24):6191-204
references: 22025666
references: Br J Pharmacol. 2012 Sep;167(1):1-12
references: 22486393
references: Exp Physiol. 2012 Dec;97(12):1292-304
references: 22581746
references: Hypertension. 2013 Jan;61(1):180-6
references: 23150514
references: Am J Physiol Heart Circ Physiol. 2013 Jan 1;304(1):H142-53
references: 23086992
references: Am J Physiol Heart Circ Physiol. 2013 Jun 1;304(11):H1547-57
references: 23564306
references: Am J Physiol Heart Circ Physiol. 2014 Jul 15;307(2):H242-51
references: 24816260
references: Hypertension. 2000 Aug;36(2):259-63
references: 10948087
references: J Physiol. 2001 Mar 1;531(Pt 2):445-58
references: 11230517
references: Am J Physiol Heart Circ Physiol. 2001 May;280(5):H2371-9
references: 11299244
references: JAMA. 2001 Apr 25;285(16):2055-7
references: 11311074
references: Biochem J. 2001 Aug 1;357(Pt 3):593-615
references: 11463332
references: Brain Res Bull. 2002 Jan 15;57(2):171-7
references: 11849823
references: J Cardiopulm Rehabil. 2002 May-Jun;22(3):178-83
references: 12042686
references: Auton Neurosci. 2002 Jun 28;98(1-2):64-9
references: 12144043
references: Circulation. 2004 May 18;109(19):2357-62
references: 15117836
references: Am J Physiol Heart Circ Physiol. 2004 Nov;287(5):H1944-9
references: 15475528
references: Exp Physiol. 2013 Sep;98(9):1337-48
references: 23771911
references: Am J Physiol Heart Circ Physiol. 2013 Nov 15;305(10):H1548-54
references: 24014673
references: Am J Physiol Heart Circ Physiol. 2014 Jan 1;306(1):H132-41
references: 24163081
references: Hypertension. 2014 Feb;63(2):324-9
references: 24191284
references: Am J Hypertens. 2004 Jan;17(1):63-70
references: 14700515
references: Curr Opin Immunol. 2004 Feb;16(1):42-7
references: 14734109
references: Circ Res. 2004 Oct 29;95(9):937-44
references: 15459075
references: J Physiol. 1972 Jul;224(1):173-86
references: 5039977
references: J Physiol. 1972 Oct;226(1):173-90
references: 4263680
references: J Comp Neurol. 1979 Jul 15;186(2):117-31
references: 447880
references: Circ Res. 2002 Nov 29;91(11):1038-45
references: 12456490
references: J Appl Physiol (1985). 2003 Apr;94(4):1437-45
references: 12482762
references: J Appl Physiol (1985). 2003 Aug;95(2):577-83
references: 12716867
references: Appl Physiol Nutr Metab. 2013 Feb;38(2):209-15
references: 23438234
references: Hypertension. 2013 Jun;61(6):1263-9
references: 23547240
references: Hypertension. 2013 Jun;61(6):1360-83
references: 23608661
references: Circ Res. 1981 Jun;48(6 Pt 2):I48-62
references: 7226464
references: Annu Rev Physiol. 1983;45:229-42
references: 6342515
references: Jpn Circ J. 1983 Jul;47(7):802-9
references: 6864984
references: J Physiol. 1983 Sep;342:383-97
references: 6631740
references: J Appl Physiol Respir Environ Exerc Physiol. 1984 Sep;57(3):644-50
references: 6092310
references: Cardiovasc Res. 1984 Nov;18(11):663-8
references: 6498873
references: J Appl Physiol (1985). 1985 Aug;59(2):459-67
references: 4030598
references: Circ Res. 1986 Dec;59(6):645-54
references: 3545533
references: Herz. 1987 Apr;12(2):119-24
references: 2953661
references: J Appl Physiol (1985). 1988 Jun;64(6):2306-13
references: 3136123
references: Circ Res. 1989 Mar;64(3):592-9
references: 2917383
references: Neuroscience. 1989;30(2):283-95
references: 2747918
references: Am J Cardiol. 1990 Mar 1;65(9):583-9
references: 2178382
references: J Appl Physiol (1985). 1990 Mar;68(3):861-7
references: 2111312
references: Am J Physiol. 1990 Nov;259(5 Pt 2):H1380-8
references: 2240239
references: Am J Physiol. 1991 Nov;261(5 Pt 2):R1307-12
references: 1951780
references: Cardiologia. 1991 Nov;36(11):867-77
references: 1817759
references: N Engl J Med. 1993 Dec 2;329(23):1677-83
references: 8232456
references: N Engl J Med. 1993 Dec 30;329(27):2002-12
references: 7504210
references: J Appl Physiol (1985). 1994 Mar;76(3):1077-81
references: 8005848
references: Am J Physiol. 1994 Aug;267(2 Pt 2):H821-7
references: 8067438
references: J Neurophysiol. 1994 Jul;72(1):63-71
references: 7965033
references: Blood Press Suppl. 1994;5:21-6
references: 7889197
references: Neuroscience. 1995 Sep;68(2):445-53
references: 7477955
references: Cardiol Clin. 1996 May;14(2):263-70
references: 8724558
references: J Comp Neurol. 1996 Jan 1;364(1):51-67
references: 8789275
references: J Chem Neuroanat. 1998 Jul;15(1):27-40
references: 9710147
references: Metabolism. 1998 Sep;47(9):1075-82
references: 9751236
references: J Hypertens. 1998 Dec;16(12 Pt 2):1993-9
references: 9886888
references: Hypertension. 1999 Apr;33(4):937-42
references: 10205227
references: Free Radic Biol Med. 2005 Feb 15;38(4):450-62
references: 15649647
references: Curr Hypertens Rep. 2005 Apr;7(2):135-40
references: 15748539
references: Am J Physiol Heart Circ Physiol. 2005 May;288(5):H2068-76
references: 15604127
references: Am J Physiol Heart Circ Physiol. 2006 Mar;290(3):H1214-9
references: 16258028
references: Am J Physiol Heart Circ Physiol. 2006 Jun;290(6):H2239-46
references: 16399856
references: Cardiovasc Res. 2006 Jul 15;71(2):247-58
references: 16765337
references: Antioxid Redox Signal. 2006 Sep-Oct;8(9-10):1583-96
references: 16987013
references: Hypertension. 2006 Oct;48(4):637-43
references: 16940212
references: J Physiol. 2006 Dec 15;577(Pt 3):1009-20
references: 17023501
references: Am J Physiol Heart Circ Physiol. 2007 Nov;293(5):H2995-3000
references: 17766474
references: Am J Physiol Heart Circ Physiol. 2008 Jun;294(6):H2693-700
references: 18441194
references: Am J Physiol Heart Circ Physiol. 2008 Oct;295(4):H1429-38
references: 18641268
references: Auton Neurosci. 2008 Nov 3;142(1-2):20-4
references: 18650132
references: Eur J Appl Physiol. 2009 Feb;105(3):351-6
references: 18989694
references: Am J Physiol Heart Circ Physiol. 2010 Nov;299(5):H1318-27
references: 20802135
references: Am J Physiol Heart Circ Physiol. 2011 Mar;300(3):H968-77
references: 21217062
references: J Physiol. 2011 Mar 1;589(Pt 5):1209-20
references: 21224235
references: Am J Physiol Heart Circ Physiol. 2011 Oct;301(4):H1191-204
references: 21841019