Long-term effects of the PPAR gamma activator pioglitazone on cardiac inflammation in stroke-prone spontaneously hypertensive rats.
We investigated the long-term effects of the thiazolidinedione PPARgamma activator pioglitazone on cardiac inflammation in stroke-prone spontaneously hypertensive rats (SHRSP), a model of malignant of hypertension. Six-week-old SHRSP were treated with pioglitazone (10 mg/kg per day p.o.) for 20 weeks. The rise in systolic blood pressure (SBP) in SHRSP was only transiently and slightly attenuated by pioglitazone (P < 0.05). On one hand, cardiac hypertrophy was little affected by the pioglitazone treatment, and there was only a reduction of subepicardial interstitial fibrosis. On the other hand, left ventricular NFkappaB and AP-1 binding activities, the expression of TNFalpha, and the adhesion of molecule PECAM were significantly decreased by pioglitazone treatment. Expression of the pro-apoptotic proteins p53 and bax was significantly increased by pioglitazone. Thus, pioglitazone-attenuated cardiac inflammation in SHRSP had little effect on BP or cardiac hypertrophy. PPARgamma activation may play a preventive cardiovascular role by offsetting the cardiac inflammatory response as demonstrated in this genetic model of malignant hypertension.
Diep
Quy N
QN
CIHR Multidisciplinary Research Group on Hypertension, Clinical Research Institute of Montreal, QC, Canada.
Amiri
Farhad
F
Benkirane
Karim
K
Paradis
Pierre
P
Schiffrin
Ernesto L
EL
D000818:Animals; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D017379:Hypertrophy, Left Ventricular / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008297:Male; D009205:Myocarditis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D047495:PPAR gamma / Q000819:agonists / Q000378:metabolism*; D000077205:Pioglitazone; D051381:Rats; D011918:Rats, Inbred SHR; D020521:Stroke / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045162:Thiazolidinediones / Q000494:pharmacology / Q000627:therapeutic use*; D013997:Time Factors
D047495:PPAR gamma; D045162:Thiazolidinediones; D000077205:Pioglitazone