title: Structure, endothelial function, cell growth, and inflammation in blood vessels of angiotensin II-infused rats: role of peroxisome proliferator-activated receptor-gamma.
abstract: BACKGROUND
  Pioglitazone and rosiglitazone, thiazolidinedione peroxisome proliferator-activated receptor-gamma (PPARgamma) activators, reduce blood pressure (BP) in some hypertensive models by unclear mechanisms. We tested the hypothesis that pioglitazone or rosiglitazone would prevent BP elevation and vascular dysfunction in angiotensin (Ang) II-infused rats by direct vascular effects.
  
  
  RESULTS
  Sprague-Dawley rats received Ang II (120 ng x kg(-1) x min(-1) SC) with or without pioglitazone (10 mg x kg(-1) x d(-1)) or rosiglitazone (5 mg x kg(-1) x d(-1)) for 7 days. Systolic BP, elevated in Ang II-infused rats (176+/-5 mm Hg) versus controls (109+/-2 mm Hg, P<0.01), was reduced by pioglitazone (134+/-2 mm Hg) or rosiglitazone (123+/-2 mm Hg). In mesenteric small arteries studied in a pressurized myograph, media/lumen ratio was increased (P<0.05) and acetylcholine-induced relaxation impaired in Ang II-infused rats (P<0.05); both were normalized by the thiazolidinediones. In Ang II-infused rats, vascular DNA synthesis (by 3H-thymidine incorporation); expression of cell cycle proteins cyclin D1 and cdk4, angiotensin II type 1 receptors, vascular cell adhesion molecule-1, and platelet and endothelial cell adhesion molecule; and nuclear factor-kappaB activity were increased. These changes were abrogated by pioglitazone or rosiglitazone.
  
  
  CONCLUSIONS
  Thiazolidinedione PPAR-gamma activators attenuated the development of hypertension, corrected structural abnormalities, normalized cell growth, and improved endothelial dysfunction induced by Ang II and prevented upregulation of angiotensin II type 1 receptors, cell cycle proteins, and proinflammatory mediators. Thiazolidinediones may be useful in the prevention and/or treatment of hypertension, particularly when it is associated with insulin resistance or diabetes mellitus.
authors: Canadian Institutes of Health Research Multidisciplinary Research Group on Hypertension, Montreal, Quebec, Canada.
authors: Quy N
authors: QN
authors: Diep
authors: Mohammed
authors: M
authors: El Mabrouk
authors: Jeffrey S
authors: JS
authors: Cohn
authors: Dierk
authors: D
authors: Endemann
authors: Farhad
authors: F
authors: Amiri
authors: Agostino
authors: A
authors: Virdis
authors: Mario Fritsch
authors: MF
authors: Neves
authors: Ernesto L
authors: EL
authors: Schiffrin
mesh_terms: D000450:Aldosterone / Q000097:blood; D000804:Angiotensin II / Q000008:administration & dosage*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001808:Blood Vessels / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D001835:Body Weight / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000096:biosynthesis; D002455:Cell Division / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis; D004334:Drug Administration Schedule; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D007249:Inflammation / Q000139:chemically induced* / Q000188:drug therapy / Q000378:metabolism; D007279:Injections, Subcutaneous; D008055:Lipids / Q000097:blood; D008297:Male; D016328:NF-kappa B / Q000096:biosynthesis; D000077205:Pioglitazone; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011945:Receptors, Angiotensin / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D012083:Renin / Q000097:blood; D000077154:Rosiglitazone; D013844:Thiazoles / Q000008:administration & dosage; D045162:Thiazolidinediones; D014157:Transcription Factors / Q000378:metabolism*; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D018797:Cell Cycle Proteins; D008055:Lipids; D016328:NF-kappa B; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011945:Receptors, Angiotensin; D018160:Receptors, Cytoplasmic and Nuclear; D013844:Thiazoles; D045162:Thiazolidinediones; D014157:Transcription Factors; D019010:Vascular Cell Adhesion Molecule-1; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D000077154:Rosiglitazone; D000804:Angiotensin II; D000450:Aldosterone; D003094:Collagen; D004247:DNA; D012083:Renin; D000077205:Pioglitazone