A 3-hydroxy-3-methylglutaryl co-enzyme A reductase inhibitor reduces hypertensive nephrosclerosis in stroke-prone spontaneously hypertensive rats.
BACKGROUND
Recent studies suggest that 3-hydroxy-3-methylglutaryl co-enzyme A reductase inhibitors (statins) exert their protective effects against cardiovascular diseases independently of their cholesterol-decreasing effects.


OBJECTIVE
To clarify the effect of a statin on hypertensive nephrosclerosis.


METHODS
We treated stroke-prone spontaneously hypertensive rats (spSHRs) chronically, starting at the age of 4 weeks, with cerivastatin (2 mg/kg per day by gavage) or vehicle. Physiological parameters, plasma chemistry and urine protein excretion were analysed. At 14 weeks of age, the rats had their kidneys removed for use in assays.


RESULTS
Compared with vehicle treatment, statin treatment reduced proteinuria and renal injury independently of blood pressure and cholesterol concentrations in spSHRs. Although expression of adhesion molecules and infiltration of inflammatory cells were not different whether or not cerivastatin treatment was used, renal fibrosis was significantly reduced in statin-treated spSHRs. We also found that expression of transforming growth factor-beta1 in kidneys was significantly inhibited in statin-treated spSHRs.


CONCLUSIONS
Cerivastatin prevents or retards hypertension-induced renal injury via inhibition of renal fibrosis and proteinuria. These results show the potential of statins as protective tools against proteinuric renal diseases, independent of their cholesterol-decreasing effects.
Yamashita
Tomoya
T
Division of Cardiovascular and Respiratory Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Japan.
Kawashima
Seinosuke
S
Miwa
Yoichi
Y
Ozaki
Masanori
M
Namiki
Masayuki
M
Hirase
Tetsuaki
T
Inoue
Nobutaka
N
Hirata
Ken-ichi
K
Yokoyama
Mitsuhiro
M
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D020022:Genetic Predisposition to Disease; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D006973:Hypertension / Q000150:complications*; D007249:Inflammation / Q000473:pathology; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008055:Lipids / Q000097:blood; D008297:Male; D009400:Nephrosclerosis / Q000209:etiology* / Q000473:pathology* / Q000503:physiopathology; D011507:Proteinuria / Q000652:urine; D051381:Rats; D011918:Rats, Inbred SHR / Q000235:genetics; D011921:Rats, Inbred WKY; D020521:Stroke / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000378:metabolism; D053773:Transforming Growth Factor beta1
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008055:Lipids; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1