[PPAR alpha activator fenofibrate regressed left ventricular hypertrophy and increased myocardium PPAR alpha expression in spontaneously hypertensive rats].
To investigate the effect of PPAR alpha activator fenofibrate on left ventricular hypertrophy and myocardium PPAR alpha (peroxisome proliferator-activated receptor-alpha) expression in spontaneously hypertensive rats (SHR).



Sixteen nine-week-old male spontaneously hypertensive rats were randomly divided into two groups: SHR received fenofibrate 100 mg x kg(-1) x d(-1) by oral gavage once daily for 8 weeks (SHR-F, n=8), and SHR received vechile (0.9 % saline) acted as controls (SHR, n=8). Age-matched Wistar-kyoto rats received vehicle for 8 weeks were served as negative controls (WKY, n=8). Systolic blood pressure was measured at the beginning, 2, 4, and 8 weeks of the experiment. At the end of the experiment, plasma BNP (brain natriuretic peptide)and lipid levels were measured. Left ventricular hypertrophy was accessed by pathological analysis. The expression of PPAR alpha and nuclear factor-kappa B (NF-kappa B p65) were investigated by the method of Western blotting.



Compared with SHR group, systolic blood pressure was slightly lowered in SHR-F group, but it didn't reach significant level(p>0.05). Fenofibrate administration lowered plasma BNP in SHR-F group (P<0.01). There were not much difference of plasma lipid levels between SHR-F and SHR group. Left ventricular mass index (assessed by left ventricular weight/body weight, g x kg(-1)), transdiameter of cardiomyocyte (TDM), cardiomyocyte area (CA), collagen volume fraction (CVF), and perivascular circumferential area (PVCA) decreased significantly in SHR-F group (P<0.05, P<0.01). The myocardium PPAR alpha expression increased significantly (P<0.01), and NF-kappa B p65 expression decreased significantly (P<0.01) in SHR-F group.



PPAR alpha activator fenofibrate can regress left ventricular hypertrophy and increase myocardium PPAR alpha expression in spontaneously hypertensive rats, which is perhaps independent of its lipid-lowering activity.
Chen
Hong-juan
HJ
The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China.
Chen
Jun-zhu
JZ
Wang
Xing-xiang
XX
Yu
Min
M
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D015153:Blotting, Western; D011345:Fenofibrate / Q000627:therapeutic use*; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D017379:Hypertrophy, Left Ventricular / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D008055:Lipids / Q000097:blood; D008297:Male; D009206:Myocardium / Q000378:metabolism; D020097:Natriuretic Peptide, Brain / Q000097:blood; D047493:PPAR alpha / Q000096:biosynthesis*; D011897:Random Allocation; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013997:Time Factors; D051996:Transcription Factor RelA / Q000096:biosynthesis
D008055:Lipids; D047493:PPAR alpha; D051996:Transcription Factor RelA; D020097:Natriuretic Peptide, Brain; D011345:Fenofibrate