Pressure-induced myogenic tone and role of 20-HETE in mediating autoregulation of cerebral blood flow.
While myogenic force in response to a changing arterial pressure has been described early in the 20th century, it was not until 1984 that the effect of a sequential increase in intraluminal pressure on cannulated cerebral arterial preparations was found to result in pressure-dependent membrane depolarization associated with spike generation and reduction in lumen diameter. Despite a great deal of effort by different laboratories and investigators, the identification of the existence of a mediator of the pressure-induced myogenic constriction in arterial muscle remained a challenge. It was the original finding by our laboratory that demonstrated the capacity of cerebral arterial muscle cells to express the cytochrome P-450 4A enzyme that catalyzes the formation of the potent vasoconstrictor 20-hydroxyeicosatetraenoic acid (20-HETE) from arachidonic acid, the production of which in cerebral arterial muscle cells increases with the elevation in intravascular pressure. 20-HETE activates protein kinase C and causes the inhibition of Ca(²+)-activated K(+) channels, depolarizes arterial muscle cell membrane, and activates L-type Ca(²+) channel to increase intracellular Ca(²+) levels and evoke vasoconstriction. The inhibition of 20-HETE formation attenuates pressure-induced arterial myogenic constriction in vitro and blunts the autoregulation of cerebral blood flow in vivo. We suggest that the formation and action of cytochrome P-450-derived 20-HETE in cerebral arterial muscle could play a critically important role in the control of cerebral arterial tone and the autoregulation of cerebral blood flow under physiological conditions.
Medical College of Wisconsin, Clinical and Translational Science Inst., Milwaukee, WI 53226, USA. dharder@mcw.edu
David R
DR
Harder
Jayashree
J
Narayanan
Debebe
D
Gebremedhin
D000818:Animals; D002560:Cerebrovascular Circulation / Q000502:physiology*; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000502:physiology*; D007473:Ion Channels / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D012039:Regional Blood Flow / Q000502:physiology; D014661:Vasoconstriction / Q000502:physiology*
D006893:Hydroxyeicosatetraenoic Acids; D007473:Ion Channels; C055987:20-hydroxy-5,8,11,14-eicosatetraenoic acid
Stroke. 1998 Jan;29(1):229-34
9445355
Am J Physiol. 1994 May;266(5 Pt 2):H2098-107
8203608
Circ Res. 1984 Aug;55(2):197-202
6744529
Biochem Biophys Res Commun. 2002 Aug 23;296(3):677-84
12176035
J Cereb Blood Flow Metab. 2008 Jan;28(1):111-25
17519974
Am J Physiol. 1994 May;266(5 Pt 2):H1840-5
8203583
Anal Biochem. 2001 Nov 15;298(2):327-36
11700990
AJNR Am J Neuroradiol. 2000 Oct;21(9):1574-85
11039334
Cell Mol Life Sci. 1999 Aug 15;55(10):1230-54
10487205
Med Image Anal. 2002 Dec;6(4):375-88
12426110
Stroke. 1996 May;27(5):971-9
8623121
Clin Exp Pharmacol Physiol. 2002 Jul;29(7):612-9
12060106
J Physiol. 1994 Mar 1;475(2):241-54
8021831
Circ Res. 2000 Jul 7;87(1):60-5
10884373
Br J Pharmacol. 1994 Jun;112(2):579-87
7915613
J Vasc Res. 1998 Jul-Aug;35(4):274-84
9701712
J Physiol. 1998 Mar 15;507 ( Pt 3):771-81
9508838
News Physiol Sci. 2002 Feb;17:27-31
11821533
Physiol Rev. 2003 Oct;83(4):1325-58
14506307
Pharmacogenetics. 1996 Feb;6(1):1-42
8845856
J Neurochem. 1985 Sep;45(3):805-9
4031862
Circ Res. 1964 Aug;15:SUPPL:279-87
14206315
Am J Physiol. 1995 Jul;269(1 Pt 2):H348-55
7631867
Hypertension. 1994 Jun;23(6 Pt 2):1096-105
8206600
Am J Physiol. 1991 Dec;261(6 Pt 2):H2016-23
1721502
J Biol Chem. 1998 Oct 30;273(44):29254-61
9786938
J Physiol. 1902 May 28;28(3):220-31
16992618
Am J Physiol. 1992 Aug;263(2 Pt 2):H519-25
1510149
Biochem Biophys Res Commun. 1989 Nov 30;165(1):312-8
2480124
Circ Res. 1993 Jan;72(1):126-36
8417836
Circ Res. 1991 Apr;68(4):1154-63
1901255
J Pharmacol Exp Ther. 1987 Aug;242(2):566-72
3612552
Arch Biochem Biophys. 1999 Sep 1;369(1):1-10
10462435
J Histochem Cytochem. 2004 Apr;52(4):447-54
15033996
Biochem Biophys Res Commun. 1991 Oct 31;180(2):982-7
1659408
Science. 1992 Apr 24;256(5056):532-5
1373909
Physiol Rev. 2002 Jan;82(1):131-85
11773611
Am J Physiol. 1987 Oct;253(4 Pt 2):F778-81
2444115
J Biol Chem. 2006 Jan 13;281(2):905-14
16286479
Science. 1999 Aug 20;285(5431):1276-9
10455056
J Cell Biol. 1998 Jul 27;142(2):485-97
9679146
Trends Cardiovasc Med. 1995 Jan-Feb;5(1):7-14
21232232
Am J Physiol Heart Circ Physiol. 2000 Apr;278(4):H1163-7
10749710
Acta Crystallogr D Biol Crystallogr. 2009 Oct;65(Pt 10):1013-20
19770498
Circ Res. 1996 Mar;78(3):415-23
8593700
J Pharmacol Exp Ther. 2008 Aug;326(2):614-22
18492947
Stroke. 2002 Dec;33(12):2957-64
12468797
Proc Natl Acad Sci U S A. 1985 Jul;82(14):4828-31
3860825
Gen Pharmacol. 1997 Mar;28(3):351-9
9068972
J Biol Chem. 1997 Oct 24;272(43):27345-52
9341185
Cell Mol Life Sci. 2000 Jun;57(6):884-95
10950304
J Pharmacol Exp Ther. 2005 Aug;314(2):522-32
15840765
Arch Biochem Biophys. 2003 Apr 1;412(1):34-41
12646265
Am J Physiol. 1990 Nov;259(5 Pt 2):H1586-94
2240255
Am J Physiol. 1993 Jul;265(1 Pt 2):H415-20
8342661
News Physiol Sci. 1999 Apr;14:74-80
11390824
Pflugers Arch. 1989;414 Suppl 1:S183-4
2780254