Rosiglitazone (peroxisome proliferator-activated receptor-gamma) counters hypertension and adverse cardiac and vascular remodeling in 2K1C hypertensive rats.
Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonists have been shown controlling blood pressure (BP) in spontaneously hypertensive rats and salt-sensitive hypertensive rats. The present study aims to test the hypothesis that PPAR-gamma agonist rosiglitazone has beneficial effects on cardiac and vascular adverse remodeling in a model of renovascular hypertension (two-kidneys-one-clip, 2K1C model). Wistar rats were divided into four groups (n=6): SHAM group, 2K1C, 2K1C+HYD (treated with hydralazine for 5 weeks) and 2K1C+ROSI (treated with rosiglitazone for 5 weeks). The left ventricle (LV), thoracic aorta (Ao) and common carotid artery (CCA) were analyzed. The BP did not show significant difference at the end of the experiment in groups 2K1C+ROSI, 2K1C+HYD and SHAM. The LV mass was smaller in 2K1C+ROSI compared with the other groups. The intima-media thickness was smaller in 2K1C+ROSI compared with untreated 2K1C ones, but not in 2K1C+HYD; 2K1C and 2K1C+HYD showed smaller Ao and CCA density of smooth muscle cell nuclei, and smaller surface density of the elastic lamellae than SHAM. The Ao and CCA circumferential wall tension and tensile stress were greater in 2K1C than in SHAM. Hypertrophied cardiomyocytes were seen in 2K1C, but not in 2K1C+ROSI and SHAM; 2K1C+ROSI had enhanced volume and length densities of intramyocardial arteries than 2K1C. The volume density of cardiac interstitium was greater in 2K1C and 2K1C+HYD than in SHAM. In conclusion, PPAR-gamma agonist rosiglitazone has beneficial effects controlling BP, reducing vascular adverse remodeling, and preserving intramyocardial vascularization in renovascular hypertensive rats (2K1C model).
Laboratory of Morphometry and Cardiovascular Morphology, Biomedical Centre, Institute of Biology, State University of Rio de Janeiro, Av 28 de Setembro, 87 (fds), 20551-030 Rio de Janeiro, RJ, Brazil.
Geraldo de Oliveira
Gde O
Silva-Junior
Thiago da Silva
Tda S
Torres
Leonardo de Souza
Lde S
Mendonca
Carlos Alberto
CA
Mandarim-de-Lacerda
D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000473:pathology; D017536:Carotid Artery, Common / Q000187:drug effects* / Q000473:pathology; D006978:Hypertension, Renovascular / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D007150:Immunohistochemistry; D007328:Insulin / Q000097:blood; D020738:Leptin / Q000097:blood; D008297:Male; D009206:Myocardium / Q000473:pathology*; D047495:PPAR gamma / Q000819:agonists*; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology / Q000627:therapeutic use*; D017539:Tunica Intima / Q000473:pathology
D007328:Insulin; D020738:Leptin; D047495:PPAR gamma; D045162:Thiazolidinediones; D000077154:Rosiglitazone