title: Role of blood cell-associated angiotensin II type 1 receptors in the cerebral microvascular response to ischemic stroke during angiotensin-induced hypertension.
abstract: BACKGROUND
  Angiotensin II type 1 receptor (AT1R) blockers lower the incidence of ischemic stroke in hypertensive patients and attenuate brain inflammation and injury in animal models. Although AT1R on both blood cells (BC) and vascular endothelial cells (EC) can be activated by angiotensin II (Ang II) to elicit inflammation, little is known about the relative contributions of AT1R expressed on BC and EC to the brain injury responses to ischemia and reperfusion (I/R) in the setting of angiotensin-induced hypertension.
  
  
  METHODS
  The contributions of BC- and EC-associated AT1R to I/R-induced brain inflammation and injury were evaluated using wild type (WT), AT1aR-/-, and bone marrow chimera mice with either a BC+/EC+ (WT→WT) or BC-/EC+ (AT1aR-/-→WT) distribution of AT1aR. The adhesion of leukocytes and platelets in venules, blood brain barrier (BBB) permeability and infarct volume were monitored in postischemic brain of normotensive and Ang II-induced hypertensive mice.
  
  
  RESULTS
  The inflammatory (blood cell adhesion) and injury (BBB permeability, infarct volume) responses were greatly exaggerated in the presence of Ang II-induced hypertension. The Ang II-enhanced responses were significantly blunted in AT1aR-/- mice. A similar level of protection was noted in AT1aR-/- →WT mice for BBB permeability and infarct volume, while less or no protection was evident for leukocyte and platelet adhesion, respectively.
  
  
  CONCLUSIONS
  BC- and EC-associated AT1aR are both involved in the brain injury responses to ischemic stroke during Ang II-hypertension, with EC AT1aR contributing more to the blood cell recruitment response and BC AT1aR exerting a significant influence on the BBB disruption and tissue necrosis elicited by I/R.
authors.affiliation: Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA 71130, USA.
authors.forename: Mutsumi
authors.initials: M
authors.lastname: Nagai
authors.affiliation: Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA 71130, USA.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Terao
authors.affiliation: Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA 71130, USA.
authors.forename: Shantel A
authors.initials: SA
authors.lastname: Vital
authors.affiliation: Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA 71130, USA.
authors.forename: Stephen F
authors.initials: SF
authors.lastname: Rodrigues
authors.affiliation: Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA 71130, USA.
authors.forename: Gokhan
authors.initials: G
authors.lastname: Yilmaz
authors.affiliation: Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA 71130, USA.
authors.forename: D Neil
authors.initials: DN
authors.lastname: Granger
references.citation: Int J Radiat Oncol Biol Phys. 2006 Nov 1;66(3):860-6
references.pmid: 17011458
references.citation: Cell Mol Neurobiol. 2005 Jun;25(3-4):485-512
references.pmid: 16075377
references.citation: J Cereb Blood Flow Metab. 1999 Oct;19(10):1092-8
references.pmid: 10532633
references.citation: Circulation. 2005 Apr 5;111(13):1690-6
references.pmid: 15795333
references.citation: Neuromolecular Med. 2010 Jun;12(2):193-204
references.pmid: 19579016
references.citation: FASEB J. 2002 Feb;16(2):169-76
references.pmid: 11818364
references.citation: J Cereb Blood Flow Metab. 2003 Mar;23(3):371-80
references.pmid: 12621312
references.citation: J Biol Chem. 1992 May 15;267(14):9455-8
references.pmid: 1374402
references.citation: J Cereb Blood Flow Metab. 2006 Apr;26(4):449-55
references.pmid: 16094317
references.citation: Stroke. 2005 Jun;36(6):1218-26
references.pmid: 15879332
references.citation: Circulation. 2002 Jan 29;105(4):530-6
references.pmid: 11815439
references.citation: Arterioscler Thromb Vasc Biol. 2008 Jan;28(1):90-6
references.pmid: 17962627
references.citation: Stroke. 2008 Mar;39(3):943-50
references.pmid: 18239178
references.citation: J Leukoc Biol. 2001 Aug;70(2):199-206
references.pmid: 11493611
references.citation: Am J Physiol Heart Circ Physiol. 2007 May;292(5):H2306-15
references.pmid: 17220190
references.citation: J Immunol. 2006 May 1;176(9):5577-86
references.pmid: 16622027
references.citation: Stroke. 2008 Sep;39(9):2554-9
references.pmid: 18617657
references.citation: J Cereb Blood Flow Metab. 2009 Mar;29(3):640-7
references.pmid: 19127280
references.citation: Stroke. 2009 Feb;40(2):597-603
references.pmid: 19023100
references.citation: Stroke. 2008 Sep;39(9):2560-70
references.pmid: 18635850
references.citation: J Cereb Blood Flow Metab. 1990 Mar;10(2):290-3
references.pmid: 1689322
references.citation: Microcirculation. 2010 Nov;17(8):641-9
references.pmid: 21044218
references.citation: Circulation. 2006 May 2;113(17):2105-12
references.pmid: 16636173
references.citation: Drug Discov Today. 2011 Jan;16(1-2):22-34
references.pmid: 21147255
references.citation: Neuroscience. 2010 Dec 15;171(3):852-8
references.pmid: 20870012
references.citation: Lancet. 2002 Mar 23;359(9311):995-1003
references.pmid: 11937178
references.citation: Hypertension. 2010 Jan;55(1):99-108
references.pmid: 19996062
references.citation: Circulation. 2004 Aug 17;110(7):843-8
references.pmid: 15289370
references.citation: Arterioscler Thromb Vasc Biol. 2000 Mar;20(3):645-51
references.pmid: 10712386
references.citation: Neuroscience. 2005;134(1):225-31
references.pmid: 15963646
references.citation: J Exp Med. 2007 Oct 1;204(10):2449-60
references.pmid: 17875676
references.citation: Am J Physiol Regul Integr Comp Physiol. 2009 Nov;297(5):R1526-31
references.pmid: 19759335
references.citation: Circulation. 2000 Oct 24;102(17):2118-23
references.pmid: 11044430
references.citation: Stroke. 2002 Sep;33(9):2297-303
references.pmid: 12215602
references.citation: Arterioscler Thromb Vasc Biol. 2006 Feb;26(2):313-8
references.pmid: 16254200
references.citation: Stroke. 2004 Jul;35(7):1726-31
references.pmid: 15143297
references.citation: Ann N Y Acad Sci. 2010 Oct;1207:149-54
references.pmid: 20955438
references.citation: Acta Physiol Hung. 2010 Jun;97(2):159-71
references.pmid: 20511125
references.citation: J Neuropathol Exp Neurol. 2010 Sep;69(9):896-909
references.pmid: 20720507
references.citation: Am J Physiol Gastrointest Liver Physiol. 2006 Jun;290(6):G1203-10
references.pmid: 16469824