Inhibition of the renal renin-angiotensin system and renoprotection by pitavastatin in type1 diabetes.
1. The aim of the present study was to investigate whether or not pitavastatin ameliorates diabetic nephropathy and if inhibition of the rennin-angiotensin-aldosterone system (RAAS) is associated with any renoprotective effects. Pitavastatin (10mg/ kg/day) and/or spironolactone (100mg/kg/day) were given by gavage for 3weeks to uninephrectomized rats with streptozotocin-induced diabetes. 2. Pitavastatin or spironolactone significantly reduced proteinuria and collagen deposition, and normalized creatinine clearance, serum creatinine levels and blood urea nitrogen concentrations. 3. Reverse transcription polymerase chain reaction analysis showed that the renal expression of collagenI, transforming growth factor-β and monocyte chemoattractant-1 were increased in diabetic rats and reduced by the pitavastatin and/or spironolactone treatment. 4. These agents also decreased angiotensin converting enzyme expression and aldosterone concentrations in the renal homogenate, but had no effect on blood glucose, haemoglobinA(1c) , and plasma total cholesterol, Na(+) , K(+) , aldosterone and NOx levels, or on systolic blood pressure measured by the tail-cuff method. Interestingly, cotreatment with pitavastatin and spironolactone did not result in additional normalization. 5. These results suggest that pitavastatin shows renoprotective effects against diabetic nephropathy mediated in part by inhibition of the renal RAAS, including the suppression of angiotensin-converting enzyme expression and aldosterone production.
Toba
Hiroe
H
Department of Clinical Pharmacology, Division of Pathological Sciences, Kyoto Pharmaceutical University, Kyoto, Japan. toba@mb.kyoto-phu.ac.jp
Mitani
Takuya
T
Takahashi
Tamotsu
T
Imai
Nobuyoshi
N
Serizawa
Ryoko
R
Wang
Jiahong
J
Kobara
Miyuki
M
Nakata
Tetsuo
T
D000450:Aldosterone / Q000378:metabolism; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D003928:Diabetic Nephropathies / Q000209:etiology / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D011804:Quinolines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D012084:Renin-Angiotensin System / Q000187:drug effects* / Q000502:physiology; D013148:Spironolactone / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use
D011804:Quinolines; D013148:Spironolactone; D000450:Aldosterone; D007703:Peptidyl-Dipeptidase A; C108475:pitavastatin