title: PPAR{gamma} activation prevents hypertensive remodeling of cerebral arteries and improves vascular function in female rats.
abstract: OBJECTIVE
  Previous studies have shown that peroxisome proliferator-activated receptor gamma (PPARgamma), a ligand-activated transcription factor expressed in vascular cells, is protective of the vasculature. We hypothesized that activation of PPARgamma could prevent hypertensive remodeling of cerebral arteries and improve vascular function.
  
  
  METHODS
  Ten female Sprague-Dawley rats were treated with the nitric oxide synthase inhibitor N(G)-nitro-l-arginine methyl ester (l-NAME) for 5 weeks, 8 were treated with l-NAME plus the PPARgamma activator rosiglitazone, and 8 received no treatment and served as controls. Blood pressure, myogenic activity, passive diameters and wall thickness of cerebral arteries, and brain capillary density were compared between the groups.
  
  
  RESULTS
  Treatment with l-NAME caused an increase in arterial blood pressure that was sustained with rosiglitazone treatment. l-NAME also caused inward hypertrophic remodeling and enhanced myogenic reactivity of cerebral arteries that was reversed by rosiglitazone. In addition, l-NAME hypertension caused rarefaction of brain capillaries by approximately 12%, whereas treatment with rosiglitazone increased capillary density by approximately 20%.
  
  
  CONCLUSIONS
  PPARgamma activation may be an effective and clinically relevant way to prevent hypertensive remodeling of cerebral arteries and capillary rarefaction as well as improving vascular function without affecting blood pressure.
authors.affiliation: Department of Neurology, University of Vermont, 89 Beaumont Avenue, Given C454, Burlington, VT 05405, USA. Marilyn.Cipolla@uvm.edu
authors.forename: Marilyn J
authors.initials: MJ
authors.lastname: Cipolla
authors.forename: Nicole
authors.initials: N
authors.lastname: Bishop
authors.forename: R Saman
authors.initials: RS
authors.lastname: Vinke
authors.forename: Julie A
authors.initials: JA
authors.lastname: Godfrey
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000098:blood supply / Q000503:physiopathology; D002196:Capillaries / Q000503:physiopathology; D002536:Cerebral Arteries / Q000378:metabolism / Q000503:physiopathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006973:Hypertension / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D047495:PPAR gamma / Q000819:agonists* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D007004:Hypoglycemic Agents; D047495:PPAR gamma; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D019331:NG-Nitroarginine Methyl Ester
references.citation: Hypertension. 1988 Aug;12(2):89-95
references.pmid: 3044994
references.citation: Circulation. 2009 Mar 3;119(8):1124-34
references.pmid: 19221220
references.citation: Diabetes. 2008 May;57(5):1394-404
references.pmid: 18268046
references.citation: PPAR Res. 2008;2008:527048
references.pmid: 18288290
references.citation: Circulation. 2002 May 14;105(19):2296-302
references.pmid: 12010913
references.citation: J Clin Invest. 1996 Oct 15;98(8):1897-905
references.pmid: 8878442
references.citation: J Hypertens Suppl. 1992 Dec;10(7):S71-5
references.pmid: 1291659
references.citation: Hypertension. 2008 Apr;51(4):867-71
references.pmid: 18285614
references.citation: Circ Res. 2008 Feb 15;102(3):283-94
references.pmid: 18276926
references.citation: Endocrinology. 2001 Jul;142(7):3125-34
references.pmid: 11416035
references.citation: Biomed Pharmacother. 2008 Jan;62(1):46-52
references.pmid: 17692499
references.citation: Front Biosci. 2008 Jan 01;13:1813-26
references.pmid: 17981670
references.citation: Stroke. 2004 Jul;35(7):1726-31
references.pmid: 15143297
references.citation: J Cereb Blood Flow Metab. 2010 Apr;30(4):827-36
references.pmid: 19953101
references.citation: Stroke. 2006 Mar;37(3):894-9
references.pmid: 16456123
references.citation: Hypertension. 2004 Mar;43(3):661-6
references.pmid: 14744930
references.citation: J Neurosci. 2008 Sep 10;28(37):9287-96
references.pmid: 18784309
references.citation: Stroke. 2007 Nov;38(11):3016-22
references.pmid: 17885259
references.citation: Microvasc Res. 1985 Jul;30(1):1-9
references.pmid: 4021832
references.citation: Stroke. 2009 Mar;40(3 Suppl):S92-4
references.pmid: 19064796
references.citation: Hypertension. 2008 Apr;51(4):1052-7
references.pmid: 18259042
references.citation: Drugs. 1999;59 Spec No:1-10
references.pmid: 10548386
references.citation: Hypertension. 2007 Jul;50(1):14-24
references.pmid: 17548723
references.citation: Circulation. 1987 Jun;75(6 Pt 2):V65-73
references.pmid: 3568338
references.citation: J Hypertens. 2005 May;23(5):1061-6
references.pmid: 15834293
references.citation: Brain Res. 2006 Jun 6;1093(1):208-18
references.pmid: 16696956
references.citation: Lancet. 1993 Jun 5;341(8858):1447-51
references.pmid: 8099148
references.citation: Cell Metab. 2008 Mar;7(3):215-26
references.pmid: 18316027