title: Pressed for time: the circadian clock and hypertension.
abstract: Hypertension is a major risk factor for cardiovascular disease and death. The "silent" rise of blood pressure that occurs over time is largely asymptomatic. However, its impact is deafening-causing and exacerbating cardiovascular disease, end-organ damage, and death. The present article addresses recent observations from human and animal studies that provide new insights into how the circadian clock regulates blood pressure, contributes to hypertension, and ultimately evolves vascular disease. Further, the molecular components of the circadian clock and their relationship with locomotor activity, metabolic control, fluid balance, and vascular resistance are discussed with an emphasis on how these novel, circadian clock-controlled mechanisms contribute to hypertension.
authors.affiliation: Department of Pharmacology and Toxicology, 1120 15th St., Medical College of Georgia, Augusta, GA 30912, USA. rrudic@mcg.edu
authors.forename: R Daniel
authors.initials: RD
authors.lastname: Rudic
authors.forename: David J
authors.initials: DJ
authors.lastname: Fulton
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage; D001683:Biological Clocks / Q000235:genetics; D001794:Blood Pressure / Q000187:drug effects / Q000235:genetics; D002318:Cardiovascular Diseases / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology* / Q000517:prevention & control; D002940:Circadian Rhythm / Q000235:genetics; D004195:Disease Models, Animal; D055870:Drug Chronotherapy; D004734:Energy Metabolism; D005786:Gene Expression Regulation; D006706:Homeostasis; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D009043:Motor Activity; D016896:Treatment Outcome; D014655:Vascular Resistance; D014882:Water-Electrolyte Balance
chemical_list: D000959:Antihypertensive Agents
references.citation: J Neurosci. 2006 Nov 8;26(45):11615-23
references.pmid: 17093083
references.citation: Circulation. 2007 Apr 24;115(16):2188-95
references.pmid: 17404161
references.citation: J Clin Invest. 2009 Aug;119(8):2423-34
references.pmid: 19587447
references.citation: Gen Pharmacol. 2000 Dec;35(6):319-23
references.pmid: 11922962
references.citation: Methods Enzymol. 2005;393:524-39
references.pmid: 15817310
references.citation: Nat Rev Genet. 2008 Oct;9(10):764-75
references.pmid: 18802415
references.citation: Hypertension. 1987 Oct;10(4):417-24
references.pmid: 3653970
references.citation: Circulation. 2008 Nov 18;118(21):2166-73
references.pmid: 18981300
references.citation: N Engl J Med. 1991 Oct 3;325(14):986-90
references.pmid: 1886635
references.citation: Physiol Behav. 2006 Jun 15;88(1-2):95-100
references.pmid: 16643970
references.citation: Genes Dev. 2006 Jul 15;20(14):1868-73
references.pmid: 16847346
references.citation: Nature. 2005 Oct 27;437(7063):1257-63
references.pmid: 16251950
references.citation: J Clin Invest. 2005 Jul;115(7):1942-52
references.pmid: 16007257
references.citation: Circulation. 2001 Oct 9;104(15):1746-8
references.pmid: 11591607
references.citation: Cell. 2002 May 17;109(4):497-508
references.pmid: 12086606
references.citation: Kidney Blood Press Res. 2007;30(3):182-6
references.pmid: 17536225
references.citation: J Neurosci. 1995 May;15(5 Pt 1):3526-38
references.pmid: 7751928
references.citation: Cell Metab. 2008 Dec;8(6):482-91
references.pmid: 19041764
references.citation: Hypertension. 2006 Apr;47(4):778-84
references.pmid: 16505205
references.citation: Hypertension. 2008 Feb;51(2):521-7
references.pmid: 18086951
references.citation: Am J Physiol Heart Circ Physiol. 2008 Feb;294(2):H810-20
references.pmid: 18055517
references.citation: J Appl Physiol (1985). 2004 Apr;96(4):1406-14
references.pmid: 14660513
references.citation: Diabet Med. 2000 May;17(5):360-4
references.pmid: 10872534
references.citation: Circulation. 2001 Feb 13;103(6):806-12
references.pmid: 11171787
references.citation: Circ Res. 2001 Jun 8;88(11):1142-50
references.pmid: 11397780
references.citation: Circulation. 1997 Feb 4;95(3):588-93
references.pmid: 9024144
references.citation: Arterioscler Thromb Vasc Biol. 2005 Aug;25(8):1610-6
references.pmid: 15947245
references.citation: Exp Nephrol. 1996 May-Jun;4(3):166-71
references.pmid: 8773479
references.citation: Nat Neurosci. 2005 Apr;8(4):476-83
references.pmid: 15750589
references.citation: Lancet. 1998 Jun 13;351(9118):1755-62
references.pmid: 9635947
references.citation: Cell. 1991 Oct 4;67(1):213-24
references.pmid: 1655275
references.citation: Hypertension. 2001 Oct;38(4):852-7
references.pmid: 11641298
references.citation: Nat Neurosci. 2007 May;10(5):543-5
references.pmid: 17417633
references.citation: Exp Physiol. 2009 Jun;94(6):648-58
references.pmid: 19218356
references.citation: Am J Physiol Heart Circ Physiol. 2007 Oct;293(4):H2543-9
references.pmid: 17704284
references.citation: Cell. 2007 May 4;129(3):605-16
references.pmid: 17482552
references.citation: Nature. 2002 May 2;417(6884):78-83
references.pmid: 11967526
references.citation: Hypertens Res. 2005 Apr;28(4):301-6
references.pmid: 16138559
references.citation: Hypertension. 1993 Feb;21(2):227-35
references.pmid: 8428785
references.citation: Chronobiol Int. 1998 Mar;15(2):135-45
references.pmid: 9562918
references.citation: Pharmacogenetics. 2002 Jan;12(1):55-65
references.pmid: 11773865
references.citation: Eur J Clin Invest. 2007 Sep;37(9):709-14
references.pmid: 17696960
references.citation: Circulation. 2005 Oct 25;112(17):2716-24
references.pmid: 16230482
references.citation: Hypertension. 2001 Dec 1;38(6):E28-32
references.pmid: 11751742
references.citation: J Clin Invest. 1996 Apr 15;97(8):1916-23
references.pmid: 8621776
references.citation: J Cereb Blood Flow Metab. 2006 Jan;26(1):58-67
references.pmid: 15959462
references.citation: Science. 1995 Jul 28;269(5223):543-6
references.pmid: 7624777
references.citation: J Diabetes Complications. 2001 Mar-Apr;15(2):75-9
references.pmid: 11274903
references.citation: J Cardiovasc Pharmacol. 1991 Mar;17(3):494-503
references.pmid: 1711613
references.citation: Stroke. 2005 Feb;36(2):342-7
references.pmid: 15637328
references.citation: Physiol Genomics. 2007 Sep 19;31(1):86-95
references.pmid: 17550994
references.citation: Br J Rheumatol. 1991 Apr;30(2):138-40
references.pmid: 1849434
references.citation: Ann N Y Acad Sci. 1996 Aug 15;783:242-53
references.pmid: 8853646
references.citation: J Mol Cell Cardiol. 2002 Feb;34(2):223-31
references.pmid: 11851361
references.citation: J Physiol. 2005 Jul 1;566(Pt 1):213-24
references.pmid: 15860530
references.citation: J Clin Invest. 1997 Sep 15;100(6):1623-33
references.pmid: 9294131
references.citation: Neuron. 2006 May 4;50(3):465-77
references.pmid: 16675400
references.citation: Science. 2005 May 13;308(5724):1043-5
references.pmid: 15845877
references.citation: Brain Res. 1994 Mar 14;639(2):217-27
references.pmid: 8205475
references.citation: Proc Natl Acad Sci U S A. 2007 Feb 27;104(9):3342-7
references.pmid: 17360649
references.citation: Proc Soc Exp Biol Med. 1979 May;161(1):78-81
references.pmid: 441075
references.citation: Diabetes Care. 1991 Mar;14(3):173-94
references.pmid: 2044434
references.citation: Am J Physiol. 1977 May;232(5):C165-73
references.pmid: 324293
references.citation: Science. 2001 Jan 19;291(5503):490-3
references.pmid: 11161204
references.citation: J Hypertens. 2000 Jul;18(7):955-61
references.pmid: 10930194
references.citation: Genes Dev. 2000 Dec 1;14(23):2950-61
references.pmid: 11114885
references.citation: Proc Natl Acad Sci U S A. 1990 Aug;87(16):6200-3
references.pmid: 2166949
references.citation: Proc Natl Acad Sci U S A. 2002 Apr 16;99(8):5721-6
references.pmid: 11960027
references.citation: Am J Hypertens. 1992 Jun;5(6 Pt 1):339-44
references.pmid: 1524757
references.citation: PLoS Biol. 2009 Mar 10;7(3):e52
references.pmid: 19278294
references.citation: Brain Res. 1998 Jun 29;797(2):287-94
references.pmid: 9666150
references.citation: N Engl J Med. 1997 Apr 17;336(16):1117-24
references.pmid: 9099655
references.citation: Hypertension. 2002 Feb;39(2):214-8
references.pmid: 11847186
references.citation: Cell. 1997 Sep 19;90(6):1003-11
references.pmid: 9323128
references.citation: Rom J Physiol. 2000 Jan-Dec;37(1-4):23-38
references.pmid: 12413144
references.citation: J Comp Neurol. 2001 Mar 12;431(3):320-30
references.pmid: 11170008
references.citation: Hypertension. 2004 Feb;43(2):192-7
references.pmid: 14732734
references.citation: J Hypertens. 2002 May;20(5):865-70
references.pmid: 12011646
references.citation: Am J Kidney Dis. 1999 Jan;33(1):29-35
references.pmid: 9915264
references.citation: J Appl Physiol. 1968 Aug;25(2):109-14
references.pmid: 5666083
references.citation: Science. 2006 Nov 24;314(5803):1304-8
references.pmid: 17124323
references.citation: Proc Natl Acad Sci U S A. 1985 Jun;82(12):4277-81
references.pmid: 3858881
references.citation: Chronobiol Int. 2001 Nov;18(6):973-85
references.pmid: 11777084
references.citation: Hypertension. 1996 Jan;27(1):130-5
references.pmid: 8591875
references.citation: Circulation. 2008 Apr 22;117(16):2087-95
references.pmid: 18413500
references.citation: Proc Natl Acad Sci U S A. 2007 Dec 26;104(52):20702-7
references.pmid: 18093917
references.citation: Circulation. 2009 Mar 24;119(11):1510-7
references.pmid: 19273720
references.citation: FEBS Lett. 2006 Jan 9;580(1):127-30
references.pmid: 16343493
references.citation: Diabetologia. 2004 Aug;47(8):1425-36
references.pmid: 15309293
references.citation: Res Commun Mol Pathol Pharmacol. 1997 Jun;96(3):319-28
references.pmid: 9261891
references.citation: J Hypertens. 2003 Jun;21(6):1107-15
references.pmid: 12777947
references.citation: Nature. 1998 Oct 22;395(6704):763-70
references.pmid: 9796811
references.citation: JAMA. 2003 May 21;289(19):2560-72
references.pmid: 12748199
references.citation: Chronobiol Int. 2003 Nov;20(6):921-62
references.pmid: 14680136
references.citation: Neuron. 1998 Jun;20(6):1103-10
references.pmid: 9655499
references.citation: Diabetes Care. 1999 Jul;22(7):1151-7
references.pmid: 10388981
references.citation: Endocrine. 2005 Jul;27(2):101-10
references.pmid: 16217123
references.citation: Am J Physiol. 1999 Dec;277(6):C1177-83
references.pmid: 10600769
references.citation: Cardiovasc Res. 1995 Nov;30(5):682-8
references.pmid: 8595613
references.citation: Hypertension. 2009 Feb;53(2):387-92
references.pmid: 19029483
references.citation: Proc Natl Acad Sci U S A. 2007 Feb 27;104(9):3450-5
references.pmid: 17360665
references.citation: Clin Nephrol. 1995 Jun;43(6):382-7
references.pmid: 7554522
references.citation: Am J Physiol. 1999 Feb;276(2):R500-4
references.pmid: 9950930
references.citation: J Am Coll Cardiol. 2002 Dec 4;40(11):2039-43
references.pmid: 12475467
references.citation: N Engl J Med. 1996 Feb 8;334(6):374-81
references.pmid: 8538710
references.citation: N Engl J Med. 2001 Jan 4;344(1):3-10
references.pmid: 11136953
references.citation: Chronobiol Int. 1996 Dec;13(6):465-75
references.pmid: 8974192
references.citation: Chronobiol Int. 1999 May;16(3):293-303
references.pmid: 10373099
references.citation: J Physiol. 2003 May 15;549(Pt 1):313-25
references.pmid: 12665600
references.citation: Lancet. 1988 Aug 13;2(8607):397
references.pmid: 2899801
references.citation: Circulation. 2009 Oct 27;120(17):1714-21
references.pmid: 19858424
references.citation: Neuroscience. 2008 Jun 23;154(2):839-47
references.pmid: 18479832
references.citation: Hypertension. 2009 Feb;53(2):381-6
references.pmid: 19104000
references.citation: Brain Res. 1997 Jul 11;762(1-2):185-94
references.pmid: 9262172
references.citation: Circulation. 1997 Sep 16;96(6):1859-62
references.pmid: 9323073
references.citation: Clin Exp Hypertens. 2005 Feb-Apr;27(2-3):307-11
references.pmid: 15835394
references.citation: Hypertension. 2002 Dec;40(6):827-33
references.pmid: 12468565
references.citation: Hypertension. 1997 Aug;30(2 Pt 1):163-7
references.pmid: 9260975
references.citation: Hypertension. 2008 Apr;51(4):827-8
references.pmid: 18316650
references.citation: J Biol Chem. 1998 Oct 16;273(42):27039-42
references.pmid: 9765215
references.citation: J Neurosci. 1991 Mar;11(3):846-51
references.pmid: 2002363
references.citation: Am J Physiol Regul Integr Comp Physiol. 2004 Jan;286(1):R108-13
references.pmid: 12969876
references.citation: Kidney Int. 2005 Apr;67(4):1410-9
references.pmid: 15780093
references.citation: Nat Struct Mol Biol. 2009 May;16(5):462-7
references.pmid: 19421159
references.citation: Clin Exp Pharmacol Physiol. 2008 Apr;35(4):391-5
references.pmid: 18307727
references.citation: Circ Res. 2008 Mar 14;102(5):607-14
references.pmid: 18218984
references.citation: N Engl J Med. 2000 Jan 20;342(3):145-53
references.pmid: 10639539
references.citation: Chronobiol Int. 2002 Mar;19(2):393-404
references.pmid: 12025932
references.citation: Proc Natl Acad Sci U S A. 2007 Oct 2;104(40):15899-904
references.pmid: 17895391
references.citation: Pharmacol Ther. 2006 Sep;111(3):629-51
references.pmid: 16480770
references.citation: Neuron. 1997 Jul;19(1):91-102
references.pmid: 9247266
references.citation: Am J Physiol Regul Integr Comp Physiol. 2008 May;294(5):R1427-34
references.pmid: 18305025
references.citation: Int J Cardiol. 2006 Mar 8;107(3):343-9
references.pmid: 16503256
references.citation: Behav Genet. 2006 Mar;36(2):301-8
references.pmid: 16408247
references.citation: Am J Physiol Renal Physiol. 2008 Oct;295(4):F1230-8
references.pmid: 18701622
references.citation: Neuroreport. 1992 Sep;3(9):809-12
references.pmid: 1421139
references.citation: Cardiovasc Res. 2009 Jan 1;81(1):28-37
references.pmid: 18806277
references.citation: Am J Physiol. 1987 Nov;253(5 Pt 2):H1074-82
references.pmid: 2825543
references.citation: Proc Natl Acad Sci U S A. 2007 Sep 4;104(36):14412-7
references.pmid: 17728404
references.citation: Am J Hypertens. 1995 Jul;8(7):719-26
references.pmid: 7546498
references.citation: Hypertension. 1999 Nov;34(5):1066-72
references.pmid: 10567183
references.citation: Hypertension. 2000 Jan;35(1 Pt 2):403-8
references.pmid: 10642332
references.citation: Cardiovasc Res. 2005 Sep 1;67(4):723-35
references.pmid: 15885672
references.citation: Am J Physiol Regul Integr Comp Physiol. 2005 Mar;288(3):R685-91
references.pmid: 15550620
references.citation: Lancet. 1978 Apr 15;1(8068):795-7
references.pmid: 85815
references.citation: Nature. 1991 Oct 10;353(6344):521-9
references.pmid: 1656270
references.citation: Endocrinology. 2008 Jul;149(7):3576-80
references.pmid: 18403480
references.citation: J Biol Rhythms. 1999 Feb;14(1):20-7
references.pmid: 10036989
references.citation: Nature. 2002 May 23;417(6887):405-10
references.pmid: 12024206
references.citation: J Hypertens. 1999 Feb;17(2):211-20
references.pmid: 10067790
references.citation: Am J Physiol Heart Circ Physiol. 2007 Aug;293(2):H1083-9
references.pmid: 17449556
references.citation: Chronobiol Int. 2004 Mar;21(2):277-96
references.pmid: 15332347
references.citation: Hypertension. 2003 Aug;42(2):189-94
references.pmid: 12835331
references.citation: Am J Physiol Heart Circ Physiol. 2008 Oct;295(4):H1634-41
references.pmid: 18708447